1.
Phencyclidine
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Phencyclidine, also known as angel dust and Sernyl among others, is a dissociative drug. PCP was brought to market in the 1950s as a pharmaceutical drug but was taken off the market in 1965 due to the high prevalence of dissociative hallucinogenic side effects. Moreover, the discovery of ketamine by Parke-Davis researchers was thought to represent an alternative for use as an anesthetic medication. Since this time a number of derivatives of PCP have been sold as dissociative drugs for recreational and non-medical use. In chemical structure, PCP is a member of the arylcyclohexylamine class, PCP works primarily as an NMDA receptor antagonist. As an addictive drug, PCP is associated with compulsive abuse, as a recreational drug, PCP may be ingested orally, smoked, insufflated or injected. PCP began to emerge as a drug in major cities in the United States in 1967. In 1978, People magazine and Mike Wallace of 60 Minutes called PCP the countrys number one drug problem, although recreational use of the drug had always been relatively low, it began declining significantly in the 1980s. In surveys, the number of school students admitting to trying PCP at least once fell from 13% in 1979 to less than 3% in 1990. PCP comes in powder and liquid forms, but typically it is sprayed onto leafy material such as cannabis, mint, oregano, tobacco, parsley, or ginger leaves. PCP is a Schedule II substance in the United States and its ACSCN is 7471 and its manufacturing quota for 2014 was 19 grams. It is a Schedule I drug by the Controlled Drugs and Substances act in Canada, a List I drug of the Opium Law in the Netherlands, PCP can be ingested through smoking. Fry is a term for marijuana or tobacco cigarettes that are dipped in PCP. PCP hydrochloride can be insufflated, depending upon the purity, the free base is quite hydrophobic and may be absorbed through skin and mucus membranes. Behavioral effects can vary by dosage, low doses produce a numbness in the extremities and intoxication, characterized by staggering, unsteady gait, slurred speech, bloodshot eyes, and loss of balance. Moderate doses will produce analgesia and anesthesia, high doses may lead to convulsions. Users frequently do not know how much of the drug they are taking due to the tendency of the drug to be produced illegally in uncontrolled conditions, psychological effects include severe changes in body image, loss of ego boundaries, paranoia, and depersonalization. Hallucinations, euphoria, and suicidal impulses are also reported, as well as aggressive behavior
2.
Pharmaceutical drug
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A pharmaceutical drug is a drug used to diagnose, cure, treat, or prevent disease. Drug therapy is an important part of the field and relies on the science of pharmacology for continual advancement. Drugs are classified in various ways, one of the key divisions is by level of control, which distinguishes prescription drugs from over-the-counter drugs. Other ways to classify medicines are by mode of action, route of administration, biological system affected, an elaborate and widely used classification system is the Anatomical Therapeutic Chemical Classification System. The World Health Organization keeps a list of essential medicines, Drug discovery and drug development are complex and expensive endeavors undertaken by pharmaceutical companies, academic scientists, and governments. Governments generally regulate what drugs can be marketed, how drugs are marketed, controversies have arisen over drug pricing and disposal of used drugs. In the US, a drug is, A substance recognized by an official pharmacopoeia or formulary, a substance intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease. A substance intended to affect the structure or any function of the body, a substance intended for use as a component of a medicine but not a device or a component, part or accessory of a device. Pharmaceutical or a drug is classified on the basis of their origin, Drug from natural origin, Herbal or plant or mineral origin, some drug substances are of marine origin. Drug from chemical as well as origin, Derived from partial herbal and partial chemical synthesis Chemical. Drug derived from animal origin, For example, hormones, Drug derived from microbial origin, Antibiotics Drug derived by biotechnology genetic-engineering, hybridoma technique for example Drug derived from radioactive substances. An elaborate and widely used system is the Anatomical Therapeutic Chemical Classification System. The World Health Organization keeps a list of essential medicines, the main classes of painkillers are NSAIDs, opioids and Local anesthetics. For consciousness Some anesthetics include Benzodiazepines and Barbiturates, the main categories of drugs for musculoskeletal disorders are, NSAIDs, muscle relaxants, neuromuscular drugs, and anticholinesterases. Euthanasia is not permitted by law in countries, and consequently medicines will not be licensed for this use in those countries. Administration is the process by which a patient takes a medicine, there are three major categories of drug administration, enteral, parenteral, and other. It can be performed in various forms such as pills, tablets. There are many variations in the routes of administration, including intravenous and they can be administered all at once as a bolus, at frequent intervals or continuously
3.
Parke-Davis
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Parke-Davis is a subsidiary of the pharmaceutical company Pfizer. Although no longer an independent corporation, it was once Americas oldest and largest drug maker, Parke-Davis was acquired by Warner–Lambert in 1970, which in turn was bought by Pfizer in 2000. Parke-Davis and Company was founded in Detroit, Michigan by Dr. Samuel P. Duffield, in 1860 Dr. Duffield owned a small drugstore at the corner of Gratiot and Woodward Avenues. Dr. Duffield made a variety of preparations, including Hoffman’s anodyne and mercurial ointment. A partnership of Dr. Duffield and Hervey Coke Parke was formed in October 1866, Parke was a businessman looking for business opportunities and Davis an ambitious man with skills in sales. Duffield withdrew in 1869 because of health and an interest in practicing medicine. The name Parke, Davis & Company was formally adopted in 1871, in 1871 the company sent expeditions to Central and South America and the West Indies in search of medicinal plants. The company produced an herbal laxative drug Cascara found from Native Americans in the Pacific Northwest, the Parke-Davis Research Laboratory is a National Historic Landmark, the surrounding Parke-Davis and Company Pharmaceutical Company Plant is on the National Register of Historic Places. The production facility on Parkdale Road in what was then Avon Township MI was also a landmark in that vicinity, Parke-Davis was acquired by Warner-Lambert in 1970. Warner-Lambert was bought by Pfizer in 2000, in the case of Franklin v. Parke-Davis the company was accused of illegal marketing practices, including the promotion of off-label uses of its anticonvulsant medication Neurontin. The drug had only approved for use in patients with epilepsy. As announced on January 22,2007, Pfizer closed its facilities in Ann Arbor. One of Parke-Davis early products was an amylase isolated from Aspergillus oryzae by Dr. Jokichi Takamine, the enzyme was originally intended for use in distilleries, but was more successfully marketed as Taka-diastase for dyspepsia. In addition, Parke-Davis distributed Coleys toxins, the first cancer vaccine, in addition, the company entered into a distribution agreement with the Inoculation Department of St Marys and distributed a number of vaccines for infectious diseases and even acne and cancer. Another of the products developed by Takamine was a pure form of adrenaline. The compound was patented in 1900 and trademarked as Adrenalin, because of the similarity of this name to Adrenaline, the use of the alternative name epinephrine for generics was mandated in the United States and is used to this day. Parke-Davis filed a lawsuit against H. K. Mulford Company alleging infringement of its Adrenalin patents, the ruling in favor of Parke-Davis by judge Learned Hand is considered crucial to modern patent law. The company promised that its products would supply the place of food, make the coward brave
4.
Ketamine
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Ketamine, sold under the brand name Ketalar among others, is a medication mainly used for starting and maintaining anesthesia. It induces a state while providing pain relief, sedation. Other uses include for chronic pain and for sedation in intensive care, heart function, breathing, and airway reflexes generally remain functional. Effects typically begin within five minutes when given by injection with the main effects lasting up to 25 minutes, common side effects include psychological reactions as the medication wears off. These reactions may include agitation, confusion, or hallucinations, elevated blood pressure and muscle tremors are relatively common, while low blood pressure and a decrease in breathing are less so. Spasms of the larynx may rarely occur, Ketamine has been classified as an NMDA receptor antagonist, it also acts on opioid receptors and monoamine transporters among others. It is on the World Health Organizations List of Essential Medicines and it is available as a generic medication. The wholesale cost in the world is between 0.08 and 0.32 USD per dose. Ketamine is also used as a recreational drug, Ketamine is frequently used in severely injured people and appears to be safe in this group. A2011 clinical practice guideline supports the use of ketamine as a sedative in emergency medicine. It is the drug of choice for people in traumatic shock who are at risk of hypotension, low blood pressure is harmful in people with severe head injury and ketamine is least likely to cause low blood pressure, often even able to prevent it. The effect of ketamine on the respiratory and circulatory systems is different from that of other anesthetics, when used at anesthetic doses, it will usually stimulate rather than depress the circulatory system. It is sometimes possible to perform ketamine anesthesia without protective measures to the airways, Ketamine is considered relatively safe because protective airway reflexes are preserved. Ketamine is used as a bronchodilator in the treatment of severe asthma, however, evidence of clinical benefit is limited. Ketamine may be used for pain management. Low doses of ketamine reduce morphine use and nausea and vomiting after surgery, high quality evidence in acute pain is insufficient to determine if ketamine is useful in this situation. It may also be used as an analgesic with opiates to manage otherwise intractable pain. It has the benefit of counteracting spinal sensitization or wind-up phenomena experienced with chronic pain
5.
Structural analog
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It can differ in one or more atoms, functional groups, or substructures, which are replaced with other atoms, groups, or substructures. A structural analog can be imagined to be formed, at least theoretically, despite a high chemical similarity, structural analogs are not necessarily functional analogs and can have very different physical, chemical, biochemical, or pharmacological properties. Chemical analogues of illegal drugs are developed and sold in order to circumvent laws, such substances are often called designer drugs. Because of this, the United States passed the Federal Analog Act in 1986 and this bill banned the production of any chemical analogue of a Schedule I or Schedule II substance that has substantially similar pharmacological effects, with the intent of human consumption
6.
Recreational drug use
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Recreational drug use is the use of a psychoactive drug to alter ones mental state in a way that modifies emotions, perceptions, and feelings for recreational purposes. When a substance enters the body, it brings on an intoxicating effect. Generally, people use drugs that fall into three categories, depressants, stimulants, and psychedelic drugs. In popular usage, it is considered to be a tolerated social behaviour rather than a serious medical condition such as self-medication. The substances classified as controlled and illegal drugs vary by country, in 2009 it was estimated that about 3% to 6% of people aged 15 to 65 had used illegal drugs at least once. International and domestic law enforcement agencies are perpetually occupied with interdiction efforts against illegal use, manufacture. Many researchers have explored the etiology of recreational drug use, there has not been agreement around any one single cause. Instead, experts tend to apply the biopsychosocial model, any number of these factors are likely to influence an individual’s drug use as they are not mutually exclusive. Regardless of genetics, mental health or traumatic experiences, social factors play a role in exposure to and availability of certain types of drugs. According to addiction researcher Martin A. Plant, many go through a period of self-redefinition before initiating recreational drug use. They tend to view using drugs as part of a lifestyle that involves belonging to a subculture that they associate with heightened status. Plant says, “From the users point of there are many positive reasons to become part of the milieu of drug taking. The reasons for drug use appear to have as much to do with needs for friendship, pleasure, becoming a drug taker, to many people, is a positive affirmation rather than a negative experience. ”Anthropological research has suggested that humansmay have evolved to counter-exploit plant neurotoxins. The ability to use chemicals to serve the function of endogenous neurotransmitters may have improved survival rates. A typically restrictive prehistoric diet may have emphasised the apparent benefit of consuming psychoactive drugs, severity and type of risks that come with recreational drug use vary widely with the drug in question and the amount being used. There are many factors in the environment and within the user interact with each drug differently. Overall, some studies suggest that alcohol is one of the most dangerous of all drugs, only heroin, crack cocaine. Researcher David Nutt stated that studies showing benefits for moderate alcohol consumption lacked control for the variable of what the subjects were drinking
7.
Hallucinogen
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A hallucinogen is a psychoactive agent which can cause hallucinations, perceptual anomalies, and other substantial subjective changes in thoughts, emotion, and consciousness. The common types of hallucinogens are psychedelics, dissociatives and deliriants, although hallucinations are a common symptom of amphetamine psychosis, amphetamines are not considered hallucinogens, as they are not a primary effect of the drugs themselves. While hallucinations can occur when abusing stimulants, the nature of stimulant psychosis is not unlike delirium, a debate persists on criteria which would easily differentiate a substance which is psychedelic from one hallucinogenic. Sir Thomas Browne in 1646 coined the term hallucination from the Latin word alucinari meaning to wander in the mind, the term psychedelic is derived from the Ancient Greek words psychē and dēloun, or mind-revealing. A hallucinogen and a psychedelic may refer correctly to the same substance, hallucinations and psychedelia may both refer to the same aspects of subjective experience in a given instance. A hallucinogen in this sense refers to any substance which causes changes in perception or hallucinations. In contrast to Hollisters original criteria, adverse effects may predominate with some hallucinogens with this application of the term, the word psychedelic was coined to express the idea of a drug that makes manifest a hidden but real aspect of the mind. One explanatory model for the experiences provoked by psychedelics is the reducing valve concept, in this view, the drugs disable the brains filtering ability to selectively prevent certain perceptions, emotions, memories and thoughts from ever reaching the conscious mind. This effect has been described as mind expanding, or consciousness expanding, many designer drugs and research chemicals are hallucinogenic in nature, such as those in the 2C and NBOMe families. Dissociatives produce analgesia, amnesia and catalepsy at anesthetic doses, dissociative symptoms include the disruption or compartmentalization of. the usually integrated functions of consciousness, memory, identity or perception. p. 523 Dissociation of sensory input can cause derealization, the perception of the world as being dream-like or unreal. The primary dissociatives achieve their effect through blocking the signals received by the NMDA receptor set and include ketamine, methoxetamine, phencyclidine, dextromethorphan, however, dissociation is also remarkably administered by salvinorin As potent κ-opioid receptor agonism. Some dissociatives can have CNS depressant effects, thereby carrying similar risks as opioids, DXM in higher doses can increase heart rate and blood pressure and still depress respiration. Inversely, PCP can have unpredictable effects and has often been classified as a stimulant. While many have reported that they feel no pain while under the effects of PCP, DXM and Ketamine, this does not fall under the usual classification of anesthetics in recreational doses. Rather, true to their name, they process pain as a kind of far away sensation, pain, although present, becomes a disembodied experience, as for probably the most common dissociative, nitrous oxide, the principal risk seems to be due to oxygen deprivation. Injury from falling is also a danger, as nitrous oxide may cause loss of consciousness. Because of the level of physical activity and relative imperviousness to pain induced by PCP
8.
Euphoria
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Euphoria is an affective state in which a person experiences pleasure or excitement and intense feelings of well-being and happiness. Certain drugs, many of which are addictive, can cause euphoria, similarly, certain natural rewards and social activities, such as aerobic exercise, laughter, listening to emotionally arousing music, music-making, and dancing, can induce a state of euphoria. Euphoria is also a symptom of certain neurological or neuropsychiatric disorders, romantic love and components of the human sexual response cycle are also associated with the induction of euphoria. According to Kent Berridge, an affective neuroscientist, intense euphoria occurs from the activation of every hedonic hotspot within the brains reward system. The word euphoria is derived from the Ancient Greek terms εὐφορία, εὖ eu meaning well and it is semantically opposite to dysphoria. A1706 English dictionary defined euphoria as the bearing of the Operation of a Medicine. A1903 article in The Boston Daily Globe refers to euphoria as pleasant excitement, in 1920 Popular Science magazine described euphoria as a high sounding name meaning feeling fit, normally making life worth living, motivating drug use, and ill formed in certain mental illnesses. In 1940 The Journal of Psychology defined euphoria as a state of well being. However, in 1957 British pharmacologist D. A. Cahal did not regard opioid euphoria as medically undesirable, the 1977 edition of A Concise Encyclopaedia of Psychiatry called euphoria a mood of contentment and well-being, with pathologic associations when used in a psychiatric context. As a sign of disease, it was described as bland and out of context. Many different types of stimuli can induce euphoria, including drugs, natural rewards. Affective disorders such as mania or bipolar disorder can involve euphoria as a symptom. Euphoria can occur as a result of dancing to music, music-making, neuroimaging studies have demonstrated that the reward system plays a central role in mediating music-induced pleasure. Pleasurable emotionally arousing music strongly increases dopamine neurotransmission in the pathways that project to the striatum. A euphoriant is a type of drug which tends to induce euphoria. Most euphoriants are addictive drugs due to their properties and ability to activate the brains reward system. Dopaminergic stimulants like amphetamine, methamphetamine, cocaine, MDMA, nicotine is a parasympathetic stimulant that acts as a mild euphoriant in some people. Certain depressants can produce euphoria, some of the euphoriant drugs in this class include drinking alcohol in moderate doses, γ-hydroxybutyric acid, some barbiturates and benzodiazepines may cause euphoria
9.
Scientific method
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The scientific method is a body of techniques for investigating phenomena, acquiring new knowledge, or correcting and integrating previous knowledge. To be termed scientific, a method of inquiry is commonly based on empirical or measurable evidence subject to specific principles of reasoning, experiments need to be designed to test hypotheses. The most important part of the method is the experiment. The scientific method is a process, which usually begins with observations about the natural world. Human beings are naturally inquisitive, so often come up with questions about things they see or hear. The best hypotheses lead to predictions that can be tested in various ways, in general, the strongest tests of hypotheses come from carefully controlled and replicated experiments that gather empirical data. Depending on how well the tests match the predictions, the hypothesis may require refinement. If a particular hypothesis becomes very well supported a theory may be developed. Although procedures vary from one field of inquiry to another, identifiable features are shared in common between them. The overall process of the method involves making conjectures, deriving predictions from them as logical consequences. A hypothesis is a conjecture, based on knowledge obtained while formulating the question, the hypothesis might be very specific or it might be broad. Scientists then test hypotheses by conducting experiments, the purpose of an experiment is to determine whether observations agree with or conflict with the predictions derived from a hypothesis. Experiments can take anywhere from a college lab to CERNs Large Hadron Collider. There are difficulties in a statement of method, however. Though the scientific method is presented as a fixed sequence of steps. Not all steps take place in scientific inquiry, and are not always in the same order. Some philosophers and scientists have argued there is no scientific method, such as Lee Smolin. Nola and Sankey remark that For some, the idea of a theory of scientific method is yester-years debate
10.
Stimulant
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Stimulants is an overarching term that covers many drugs including those that increase activity of the body, drugs that are pleasurable and invigorating, or drugs that have sympathomimetic effects. Due to their rendering a characteristic up feeling, stimulants are also referred to as uppers. Depressants or downers, which decrease mental and/or physical function, are in stark contrast to stimulants and are considered to be the functionally opposite drug class, Stimulants are widely used throughout the world as prescription medicines as well as without a prescription as performance-enhancing or recreational drugs. The most frequently prescribed stimulants as of 2013 were lisdexamfetamine, methylphenidate and it is estimated that the percent of the population that has abused amphetamines, cocaine and MDMA combined is between. 8% and 2. 1%. Stimulants in therapeutic doses, such as given to patients with ADHD, increases ability to focus, vigor, sociability, libido. However, in higher doses stimulants may actually decrease the ability to focus, in higher doses stimulants may also produce euphoria, vigor, and decrease need for sleep. Many, but not all, stimulants have ergogenic effects, Drugs such as ephedrine, pseudoephedrine, amphetamine and methylphenidate have well documented ergogenic effects, while drugs such as cocaine and methamphetamine have the opposite effect. In some cases psychiatric phenomenon may emerge such as stimulant psychosis, paranoia, acute toxicity has been reportedly associated with a homicide, paranoia, aggressive behavior, motor dysfunction, and punding. The violent and aggressive behavior associated with acute stimulant toxicity may partially be driven by paranoia, most drugs classified as stimulants are sympathomimetics, that is they stimulate the sympathetic branch of the autonomic nervous system. This leads to such as mydriasis, increased heart rate, blood pressure, respiratory rate. When these changes become pathological, they are called arrhythmia, hypertension, and hyperthermia, however given the complexity of the mechanisms that underly these potentially fatal outcomes of acute stimulant toxicity, it is impossible to determine what dose may be lethal. Assessment of the effects of stimulants is relevant given the large population currently taking stimulants. A systematic review of cardiovascular effects of prescription stimulants found no association in children, a review over a four-year period found that there were few negative effects of stimulant treatment, but stressed the need for longer term studies. A review of a long period of prescription stimulate use in those with ADHD found that cardiovascular side effects were limited to transient increases in blood pressure only. Initiation of stimulant treatment in those with ADHD in early childhood appears to carry benefits into adulthood with regard to social and cognitive functioning, Abuse of prescription stimulants or of illicit stimulants carries many negative health risks. Abuse of cocaine, depending upon route of administration, increases risk of disease, stroke. Cocaine may also increase risk for disease, as well as damage nasal cartilage. Abuse of methamphetamine produces similar effects as well as marked degeneration of dopaminergic neurons, Drugs used to treat sleep disorders such as excessive daytime sleepiness are called eugeroics, and include notable stimulants such as modafinil
11.
Analgesic
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An analgesic or painkiller is any member of the group of drugs used to achieve analgesia, relief from pain. Analgesic drugs act in various ways on the peripheral and central nervous systems and they are distinct from anesthetics, which temporarily affect, and in some instances completely eliminate, sensation. Analgesics include paracetamol, the nonsteroidal anti-inflammatory drugs such as the salicylates, when choosing analgesics, the severity and response to other medication determines the choice of agent, the World Health Organization pain ladder specifies mild analgesics as its first step. Topical nonsteroidal anti-inflammatory drugs provided pain relief in common such as muscle sprains. Since the side effects are also lesser, topical preparations could be preferred over oral medications in these conditions, each different type of analgesic has its own associated side effects. Drugs for pain are typically classified by chemical structure and they may also be classified in other ways. Sometimes they are classified by use for classes of medical condition. Other times they are sorted by the needs of populations who would use them. They might be listed by availability in an area, perhaps to prevent recommending a drug which is illegal in one place even if it is easily available elsewhere. Paracetamol, also known as acetaminophen or APAP, is a used to treat pain. It is typically used for mild to moderate pain, in combination with opioid pain medication, paracetamol is used for more severe pain such as cancer pain and after surgery. It is typically used either by mouth or rectally but is also available intravenously, effects last between two and four hours. Paracetamol is classified as a mild analgesic, paracetamol is generally safe at recommended doses. Nonsteroidal anti-inflammatory drugs, are a class that groups together drugs that provide analgesic and antipyretic effects. The most prominent members of group of drugs, aspirin. These drugs have been derived from NSAIDs, the cyclooxygenase enzyme inhibited by NSAIDs was discovered to have at least 2 different versions, COX1 and COX2. Research suggested most of the effects of NSAIDs to be mediated by blocking the COX1 enzyme. Thus, the COX2 inhibitors were developed to inhibit only the COX2 enzyme and these drugs are equally effective analgesics when compared with NSAIDs, but cause less gastrointestinal hemorrhage in particular
12.
Chemist
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A chemist is a scientist trained in the study of chemistry. Chemists study the composition of matter and its properties, chemists carefully describe the properties they study in terms of quantities, with detail on the level of molecules and their component atoms. Chemists carefully measure substance proportions, reaction rates, and other chemical properties, the word chemist is also used to address Pharmacists in Commonwealth English. Chemists may specialize in any number of subdisciplines of chemistry, materials scientists and metallurgists share much of the same education and skills with chemists. The roots of chemistry can be traced to the phenomenon of burning, fire was a mystical force that transformed one substance into another and thus was of primary interest to mankind. It was fire that led to the discovery of iron and glasses, after gold was discovered and became a precious metal, many people were interested to find a method that could convert other substances into gold. This led to the protoscience called alchemy, the word chemist is derived from the New Latin noun chimista, an abbreviation of alchimista. Alchemists discovered many chemical processes that led to the development of modern chemistry, Chemistry as we know it today, was invented by Antoine Lavoisier with his law of conservation of mass in 1783. The discoveries of the elements has a long history culminating in the creation of the periodic table by Dmitri Mendeleev. The Nobel Prize in Chemistry created in 1901 gives an excellent overview of chemical discovery since the start of the 20th century. Jobs for chemists usually require at least a degree, but many positions, especially those in research. At the Masters level and higher, students tend to specialize in a particular field, postdoctoral experience may be required for certain positions. Workers whose work involves chemistry, but not at a complexity requiring an education with a degree, are commonly referred to as chemical technicians. Such technicians commonly do such work as simpler, routine analyses for quality control or in clinical laboratories, there are also degrees specific to become a Chemical Technologist, which are somewhat distinct from those required when a student is interested in becoming a professional Chemist. A Chemical technologist is more involved in the management and operation of the equipment and they are part of the team of a chemical laboratory in which the quality of the raw material, intermediate products and finished products is analyzed. They also perform functions in the areas of quality control. The higher the level achieved in the field of Chemistry, the higher the responsibility given to that chemist. Chemistry, as a field, have so many applications that different tasks/objectives can be given to workers/scientists with these different levels of education and/or experience
13.
Cyclohexylamine
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Cyclohexylamine is an organic compound, belonging to the aliphatic amine class. It is a liquid, although like many amines, samples are often colored due to contaminants. It has an odor and is miscible with water. Like other amines, it is a base, compared to strong bases such as NaOH. It is an intermediate in the production of many other organic compounds. It is a metabolite of cyclamate, cyclohexylamine is used as an intermediate in synthesis of other organic compounds. It is the precursor to sulfenamide-based reagents used as accelerators for vulcanization and it is a building block for pharmaceuticals. The amine itself is a corrosion inhibitor. Some sweeteners are derived from this amine, notably cyclamate, the herbicide hexazinone is derived from cyclohexylamine. LD50 =0.71 ml/kg It is flammable, with point at 28.6 °C. It is toxic by ingestion and inhalation, the inhalation itself may be fatal. It readily absorbs through skin, which it irritates, cyclohexylamine is listed as an extremely hazardous substance as defined by Section 302 of the U. S. Emergency Planning and Community Right-to-Know Act and it has been used as a flushing aid in the printing ink industry
14.
Aryl
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In the context of organic molecules, aryl is any functional group or substituent derived from an aromatic ring, usually an aromatic hydrocarbon, be it phenyl, naphthyl, thienyl, indolyl, etc. Aryl is used for the sake of abbreviation or generalization, a simple aryl group is phenyl, C6H5, it is derived from benzene. The tolyl group, CH3C6H4, is derived from toluene, the xylyl group, 2C6H3, is derived from xylene, while the naphthyl group, C10H7, is derived from naphthalene. Arylation is a process in which an aryl group is attached to a substituent. Alkyl Aryl hydrocarbon receptor, a target for dioxins Arene compound
15.
Moiety (chemistry)
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In organic chemistry moiety is a term used for part of a molecule. Larger moieties are often functional groups, a functional group is a moiety that participates in similar chemical reactions in most molecules that contain it. In turn the parts of the group are termed moieties, for example, methyl p-hydroxybenzoate contains a phenol functional group within the acyl moiety, which in turn is part of the paraben moiety. Moieties that are branches extending from the backbone of a hydrocarbon molecule, which can often be broken off and substituted with others, are called substituents or side chains
16.
Geminal
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In chemistry, the term geminal refers to the relationship between two atoms or functional groups that are attached to the same atom. The word comes from Latin gemini meaning twins, a geminal diol, for example, is a diol attached to the same carbon atom, as in methanediol. The prefix gem may also be applied to a name to denote this relationship. Geminal diols, for example, are converted to ketones or aldehydes with loss of water. The following example shows the conversion of a methyl ketone to a gem-dichloride through a reaction with phosphorus pentachloride. This gem-dichloride can then be used to synthesize an alkyne, the related term vicinal refers to the relationship between two functional groups that are attached to adjacent atoms
17.
Amine
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In organic chemistry, amines are compounds and functional groups that contain a basic nitrogen atom with a lone pair. Amines are formally derivatives of ammonia, wherein one or more hydrogen atoms have been replaced by a substituent such as an alkyl or aryl group, important amines include amino acids, biogenic amines, trimethylamine, and aniline, see Category, Amines for a list of amines. Inorganic derivatives of ammonia are also called amines, such as chloramine, see Category, compounds with a nitrogen atom attached to a carbonyl group, thus having the structure R–CO–NR′R″, are called amides and have different chemical properties from amines. An aliphatic amine has no aromatic ring attached directly to the nitrogen atom, aromatic amines have the nitrogen atom connected to an aromatic ring as in the various anilines. The aromatic ring decreases the alkalinity of the amine, depending on its substituents, the presence of an amine group strongly increases the reactivity of the aromatic ring, due to an electron-donating effect. Amines are organized into four subcategories, Primary amines — Primary amines arise when one of three atoms in ammonia is replaced by an alkyl or aromatic. Important primary alkyl amines include, methylamine, most amino acids, Secondary amines — Secondary amines have two organic substituents bound to the nitrogen together with one hydrogen. Important representatives include dimethylamine, while an example of an aromatic amine would be diphenylamine, tertiary amines — In tertiary amines, nitrogen has three organic substituents. Examples include trimethylamine, which has a fishy smell. Cyclic amines — Cyclic amines are either secondary or tertiary amines, examples of cyclic amines include the 3-membered ring aziridine and the six-membered ring piperidine. N-methylpiperidine and N-phenylpiperidine are examples of tertiary amines. It is also possible to have four organic substituents on the nitrogen and these species are not amines but are quaternary ammonium cations and have a charged nitrogen center. Quaternary ammonium salts exist with many kinds of anions, Amines are named in several ways. Typically, the compound is given the prefix amino- or the suffix, the prefix N- shows substitution on the nitrogen atom. An organic compound with multiple amino groups is called a diamine, triamine, tetraamine, systematic names for some common amines, Hydrogen bonding significantly influences the properties of primary and secondary amines. Thus the melting point and boiling point of amines is higher than those of the corresponding phosphines, for example, methyl and ethyl amines are gases under standard conditions, whereas the corresponding methyl and ethyl alcohols are liquids. Amines possess a characteristic smell, liquid amines have a distinctive fishy smell. The nitrogen atom features a lone pair that can bind H+ to form an ammonium ion R3NH+
18.
Phenyl group
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In organic chemistry, the phenyl group or phenyl ring is a cyclic group of atoms with the formula C6H5. Phenyl groups are related to benzene and can be viewed as a benzene ring, minus a hydrogen. Phenyl groups have six carbon atoms bonded together in a planar ring, five of which are bonded to individual hydrogen atoms. Phenyl groups are commonplace in organic chemistry, although often depicted with alternating double and single bonds, phenyl groups are chemically aromatic and show nearly equal bond lengths between carbon atoms in the ring. Usually, a group is synonymous to C6H5– and is represented by the symbol Ph or, archaically. Benzene is sometimes denoted as PhH, Phenyl groups are generally attached to other atoms or groups. For example, triphenylmethane has three groups attached to the same carbon center. Many or even most phenyl compounds are not described with the term phenyl, for example, the chloro derivative C6H5Cl is normally called chlorobenzene, although it could be called phenyl chloride. For example, O2NC6H4 is nitrophenyl and F5C6 is pentafluorophenyl, monosubstituted phenyl groups are associated with electrophilic aromatic substitution reactions and the products follow the arene substitution pattern. So, a substituted phenyl compound has three isomers, ortho, meta and para. A disubstituted phenyl compound may be, for example,1,3, 5-trisubstituted, or 1,2, higher degrees of substitution, of which the pentafluorophenyl group is an example, exist, and are named according to IUPAC nomenclature. Phenyl compounds are derived from benzene, at least conceptually and often in terms of their production, in terms of its electronic properties, the phenyl group is related to a vinyl group. Phenyl groups tend to resist oxidation and reduction, Phenyl groups have enhanced stability in comparison to equivalent bonding in aliphatic groups. This increased stability is due to the properties of aromatic molecular orbitals. The bond lengths between carbon atoms in a group are approximately 1.4 Å. In 1H-NMR spectroscopy, protons of a group typically have chemical shifts around 7.27 ppm. These chemical shifts are influenced by aromatic ring current and may change depending on substituents, Phenyl groups are usually introduced using reagents that behave as sources of the phenyl anion or the phenyl cation. Representative reagents include phenyllithium and phenylmagnesium bromide, electrophiles attack benzene to give phenyl derivatives, C6H6 + E+ → C6H5E + H+ where E+ = Cl+, NO2+, SO3
19.
Piperidine
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Piperidine is an organic compound with the molecular formula 5NH. This heterocyclic amine consists of a ring containing five methylene bridges. It is a liquid with an odor described as objectionable. The name comes from the genus name Piper, which is the Latin word for pepper, although, piperidine is a common organic compound, it is best known as a representative structure element within many pharmaceuticals and alkaloids. Piperidine was first reported in 1850 by the Scottish chemist Thomas Anderson and again, independently, in 1852 by the French chemist Auguste Cahours, both men obtained piperidine by reacting piperine with nitric acid. Piperidine itself has been obtained from black pepper, from Psilocaulon absimile, the piperidine structural motif is present in numerous natural alkaloids. These include piperine, which gives black pepper its spicy taste and this gave the compound its name. Piperidine prefers a chair conformation, similar to cyclohexane, unlike cyclohexane, piperidine has two distinguishable chair conformations, one with the N–H bond in an axial position, and the other in an equatorial position. After much controversy during the 1950s–1970s, the equatorial conformation was found to be stable by 0.72 kcal/mol in the gas phase. In nonpolar solvents, a range between 0.2 and 0.6 kcal/mol has been estimated, but in polar solvents the axial conformer may be more stable. In the case of N-methylpiperidine, the conformation is preferred by 3.16 kcal/mol. Piperidine is a widely used secondary amine and it is widely used to convert ketones to enamines. Enamines derived from piperidine can be used in the Stork enamine alkylation reaction, Piperidine can be converted to the chloramine C5H10NCl with calcium hypochlorite. The resulting chloramine undergoes dehydrohalogenation to afford the cyclic imine, 13C NMR,47.27.2,25.2 1H NMR,2.79,2.19,1.51 Piperidine is used as a solvent and as a base. A significant industrial application of piperidine is for the production of dipiperidinyl dithiuram tetrasulfide, Piperidine and its derivatives are ubiquitous building blocks in the synthesis of pharmaceuticals and fine chemicals. Piperidine is also used as a base for the deprotection of Fmoc-amino acids used in solid-phase peptide synthesis
20.
Pyrrolidine
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Pyrrolidine, also known as tetrahydropyrrole, is an organic compound with the molecular formula 4NH. It is a secondary amine, also classified as a saturated heterocycle. It is a liquid that is miscible with water and most organic solvents. It has an ammonia-like, but characteristic odor, in addition to pyrrolidine itself, many substituted pyrrolidines are known. Pyrrolidine is produced by treatment of 1, 4-butanediol with ammonia over an oxide catalyst, many modifications of pyrrolidine are found in natural and synthetic chemistry. The pyrrolidine ring structure is present in numerous natural alkaloids such as nicotine and hygrine and it is found in many drugs such as procyclidine and bepridil. It also forms the basis for the racetam compounds, the amino acids proline and hydroxyproline are, in a structural sense, derivatives of pyrrolidine. Its basicity is typical of other dialkyl amines, relative to many secondary amines, pyrrolidine is distinctive because of its compactness, a consequence of its cyclic structure. Pyrrolidine is used as a block in the synthesis of more complex organic compounds. It is used to activate ketones and aldehydes toward nucleophilic addition by formation of enamines
21.
NMDA receptor antagonist
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NMDA receptor antagonists are a class of anesthetics that work to antagonize, or inhibit the action of, the N-Methyl-D-aspartate receptor. They are used as anesthetics for animals including humans, the state of anesthesia they induce is referred to as dissociative anesthesia, recent research conducted on primates suggests that, while very consistent and long-term ketamine use may be neurotoxic, acute use is not. Several synthetic opioids function additionally as NMDAR-antagonists, such as pethidine, methadone, dextropropoxyphene, tramadol, when used recreationally, they are classified as dissociative drugs. NMDA receptor antagonists induce a state called dissociative anesthesia, marked by catalepsy, amnesia, ketamine is a favored anesthetic for emergency patients with unknown medical history and in the treatment of burn victims because it depresses breathing and circulation less than other anesthetics. Dextrorphan, a metabolite of dextromethorphan, is known to be an NMDA receptor antagonist, depressed NMDA receptor function is associated with an array of negative symptoms. For example, NMDA receptor hypofunction that occurs as the ages may be partially responsible for memory deficits associated with aging. Schizophrenia may also have to do with irregular NMDA receptor function, increased levels of another NMDA antagonist, kynurenic acid, may aggravate the symptoms of schizophrenia, according to the kynurenic hypothesis. NMDA receptor antagonists can mimic these problems, they sometimes induce psychotomimetic side effects, because of these psychotomimetic effects, NMDA receptor antagonists, especially phencyclidine, ketamine, and dextromethorphan, are used as recreational drugs. Most NMDA receptor antagonists are metabolized in the liver, frequent administration of most NMDA receptor antagonists can lead to tolerance, whereby the liver will more quickly eliminate NMDA receptor antagonists from the bloodstream. Although NMDA antagonists were once thought to cause neurotoxicity in humans in the form of Olneys lesions. Olneys lesions involve mass vacuolization of neurons observed in rodents, however, many suggest that this is not a valid model of human use, and studies conducted on primates have shown that use must be heavy and chronic to cause neurotoxicity. Indeed, a 2009 review found no evidence of ketamine-induced neuron death in humans, however, temporary and permanent cognitive impairments have been shown to occur in long-term or heavy human users of the NMDA antagonists PCP and ketamine. A large-scale, longitudinal study found that current frequent ketamine users have modest cognitive deficits, many drugs have been found that lessen the risk of neurotoxicity from NMDA receptor antagonists. Centrally acting alpha 2 agonists such as clonidine and guanfacine are thought to most directly target the etiology of NMDA neurotoxicity. This is counterbalanced by the risk of developing Olneys lesions, which have ever been observed in rodents. These results have not yet been reproduced in humans, however, mild NMDA receptor antagonists like amitriptyline have been found to be helpful in benzodiazepine withdrawal. The NMDA receptor is a receptor that allows for the transfer of electrical signals between neurons in the brain and in the spinal column. For electrical signals to pass, the NMDA receptor must be open, to remain open, glutamate and glycine must bind to the NMDA receptor
22.
Dopamine reuptake inhibitor
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A dopamine reuptake inhibitor is a class of drug which acts as a reuptake inhibitor of the monoamine neurotransmitter dopamine by blocking the action of the dopamine transporter. Reuptake inhibition is achieved when extracellular dopamine not absorbed by the neuron is blocked from re-entering the presynaptic neuron. This results in increased concentrations of dopamine and increase in dopaminergic neurotransmission. Lack of dopamine reuptake and the increase in levels of dopamine have been linked to increased susceptibility to addictive behavior given increase in dopaminergic neurotransmission. The dopaminergic pathways are considered to be strong reward centers, many DRIs such as cocaine are drugs of abuse due to the rewarding effects evoked by elevated synaptic concentrations of dopamine in the brain. Until the 1950s, dopamine was thought to contribute to the biosynthesis of norepinephrine and epinephrine. The following drugs are or have been used but only coincidentally have DRI properties, benzatropine, diphenylpyraline, etybenzatropine, ketamine, nefopam, pethidine. The following are a selection of some particularly notably abused DRIs, cocaine, ketamine, MDPV, naphyrone, the wakefulness-promoting agent modafinil and its analogues have been approved to treat narcolepsy and shift work sleep disorder. These act as weak DRIs, but this effect does not correlate with wakefulness-promoting effects, the conclusion is these drugs promote wakefulness via some other mechanism. DRIs have been explored as potential antiaddictive agents because of their ability to replace the reward effects received from other drugs, DRIs have been successfully used to serve as nicotine replacement in cases of smoking addiction and methadone replacement in the case of heroin addiction. DRIs have been explored as treatment for addiction, and have shown to alleviate cravings. Monoamine reuptake inhibitors, including DRIs, have shown effectiveness as therapy for excessive food intake. Most drugs marketed for this purpose have been withdrawn or discontinued because of side effects such as increase in blood pressure. Only DRIs which are selective for the DAT over the other monoamine transporters are listed below, for a list of DRIs that act at multiple MATs, see other monoamine reuptake inhibitor pages such as NDRI and SNDRI
23.
Agonist
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An agonist is a chemical that binds to a receptor and activates the receptor to produce a biological response. Whereas an agonist causes an action, an antagonist blocks the action of the agonist, receptors can be activated by either endogenous or exogenous agonists, resulting in a biological response. A physiological agonist is a substance that creates the same bodily responses but does not bind to the same receptor, an endogenous agonist for a particular receptor is a compound naturally produced by the body that binds to and activates that receptor. For example, the endogenous agonist for serotonin receptors is serotonin, a superagonist is a compound that is capable of producing a greater maximal response than the endogenous agonist for the target receptor, and thus has an efficacy of more than 100%. Full agonists bind and activate a receptor, producing full efficacy at that receptor, one example of a drug that acts as a full agonist is isoproterenol, which mimics the action of adrenaline at β adrenoreceptors. Another example is morphine, which mimics the actions of endorphins at μ-opioid receptors throughout the nervous system. Partial agonists also bind and activate a receptor, but have only partial efficacy at the receptor relative to a full agonist. Agents like buprenorphine are used to treat opiate dependence for this reason, as they produce milder effects on the receptor with lower dependence. An inverse agonist is an agent that binds to the same receptor binding-site as an agonist for that receptor, inverse agonists exert the opposite pharmacological effect of a receptor agonist, not merely an absence of the agonist effect as seen with antagonist. An example is the inverse agonist rimonabant. A co-agonist works with other co-agonists to produce the desired effect together, NMDA receptor activation requires the binding of both glutamate, glycine and D-serine co-agonists. An irreversible agonist is a type of agonist that binds permanently to a receptor through the formation of covalent bonds, a few of these have been described. A selective agonist is selective for a type of receptor. E. g. buspirone is a selective agonist for serotonin 5-HT1A, terms that describe this phenomenon are functional selectivity, protean agonism, or selective receptor modulators. Potency is the amount of agonist needed to elicit a desired response, the potency of an agonist is inversely related to its EC50 value. The EC50 can be measured for a given agonist by determining the concentration of agonist needed to elicit half of the biological response of the agonist. The EC50 value is useful for comparing the potency of drugs with similar efficacies producing physiologically similar effects, the smaller the EC50 value, the greater the potency of the agonist, the lower the concentration of drug that is required to elicit the maximum biological response. This relationship, termed the index, is defined as the ratio TD50, ED50
24.
Sigma receptor
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The sigma receptors σ1 and σ2 bind to ligands such as 4-PPBP, SA4503, ditolylguanidine, dimethyltryptamine, and siramesine. However, such drugs had no clinically relevant affinities for μ, κ, however, pharmacological testing indicated that the σ-receptors were activated by drugs completely unrelated to the opioids, and their function was unrelated to the function of the opioid receptors. When the σ1 receptor was isolated and cloned, it was found to have no similarity to the opioid receptors. At this point, they were designated as a class of receptors. The function of these receptors is poorly understood though an endogenous ligand, activation of σ–receptors by an agonist ligand may induce hallucinogenic effects and also may be responsible for the paradoxical convulsions sometimes seen in opiate overdose. Drugs known to be σ–agonists include cocaine, morphine/diacetylmorphine, opipramol, PCP, fluvoxamine, methamphetamine, dextromethorphan, however the exact role of σ–receptors is difficult to establish as many σ–agonists also bind to other targets such as the κ-opioid receptor and the NMDA glutamate receptor. In animal experiments, σ–antagonists such as rimcazole were able to block convulsions from cocaine overdose, σ–antagonists are also under investigation for use as antipsychotic medications. Physiologic effects when the σ–receptor is activated include hypertonia, tachycardia, tachypnea, antitussive effects, some σ–receptor agonists—such as cocaine, a weak σ–agonist—exert convulsant effects in animals. Behavioral reactions to σ–agonists are rather heterogeneous, some individuals find σ–receptor agonists euphoric with significant anti-depressive effects, other individuals, however, experience dysphoria and often report feelings of malaise or anxiety. Recently selective σ–receptor agonists were shown to produce effects in mice. Sigma Receptor at the US National Library of Medicine Medical Subject Headings
25.
Nicotinic acetylcholine receptor
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Nicotinic acetylcholine receptors, or nAChRs, are receptor proteins that respond to the neurotransmitter acetylcholine. Nicotinic receptors also respond to drugs, including the nicotinic receptor agonist nicotine, nicotinic receptors are also found in other creatures. In insects, the system is limited to the central nervous system. The nicotinic receptors are considered cholinergic receptors, since they respond to acetylcholine, nicotinic receptors get their name from nicotine, which does not stimulate the muscarinic acetylcholine receptor, but instead selectively binds to the nicotinic receptor. The muscarinic acetylcholine receptor likewise gets its name from a chemical that selectively attaches to that receptor -- muscarine, acetylcholine itself binds to both muscarinic and nicotinic acetylcholine receptors. As ionotropic receptors, nAChRs are directly linked to ion channels, nicotinic acetylcholine receptors are the best-studied of the ionotropic receptors. Thus, for example, nicotinic receptor antagonists interfere with the baroreflex that normally corrects changes in pressure by sympathetic and parasympathetic stimulation of the heart. Nicotinic receptors, with a mass of 290 kDa, are made up of five subunits. Each subunit comprises four transmembrane domains with both the N- and C-terminus located extracellularly and they possess similarities with GABAA receptors, glycine receptors, and the type 3 serotonin receptors, or the signature Cys-loop proteins. In vertebrates, nicotinic receptors are classified into two subtypes based on their primary sites of expression, muscle-type nicotinic receptors and neuronal-type nicotinic receptors. The neuronal subtypes are various homomeric or heteromeric combinations of twelve different nicotinic receptor subunits, α2−α10, examples of the neuronal subtypes include,32,23, and 5. In both muscle-type and neuronal-type receptors, the subunits are similar to one another, especially in the hydrophobic regions. As with all ligand-gated ion channels, opening of the channel pore requires the binding of a chemical messenger. Several different terms are used to refer to the molecules that bind receptors, as well as the endogenous agonist acetylcholine, agonists of the nAChR are nicotine, epibatidine, and choline. Nicotinic antagonists that block the receptor include hexamethonium, in muscle-type nAChRs, the acetylcholine binding sites are located at the α and either ε or δ subunits interface in the extracellular domain near the N terminus. When an agonist binds to the site, all present subunits undergo a change and the channel is opened. Nicotinic AChRs may exist in different interconvertible conformational states, binding of an agonist stabilises the open and desensitised states. Opening of the channel allows positively charged ions to move across it, in particular, sodium enters the cell, the net flow of positively charged ions is inward
26.
D2 receptor
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Dopamine receptor D2, also known as D2R, is a protein that, in humans, is encoded by the DRD2 gene. The dopamine D2 receptor is the receptor for all antipsychotic drugs. This gene encodes the D2 subtype of the receptor, which is coupled to Gi subtype of G protein-coupled receptor. This G protein-coupled receptor inhibits adenylyl cyclase activity, in mice, regulation of D2R surface expression by the neuronal calcium sensor-1 in the dentate gyrus is involved in exploration, synaptic plasticity and memory formation. In flies, activation of the D2 autoreceptor protected dopamine neurons from cell death induced by a toxin mimicking Parkinsons disease pathology, alternative splicing of this gene results in three transcript variants encoding different isoforms. The long form has the sequence and functions as a classic post-synaptic receptor. The short form is pre-synaptic and functions as an autoreceptor that regulates the levels of dopamine in the synaptic cleft, agonism of D2sh receptors inhibits dopamine release, antagonism increases dopaminergic release. A third D2 form differs from the sequence where 270V is replaced by VVQ. Allelic variants, A-241G C132T, G423A, T765C, C939T, C957T, some researchers have previously associated the polymorphism Taq 1A to the DRD2 gene. However, the polymorphism resides in exon 8 of the ANKK1 gene, DRD2 TaqIA polymorphism has been reported to be associated with an increased risk for developing motor fluctuations but not hallucinations in Parkinsons disease. Several selective D2 ligands are, however, now available, uNC9994 The dopamine receptor D2 has been shown to interact with EPB41L1, PPP1R9B and NCS-1. Receptors, Dopamine D2 at the US National Library of Medicine Medical Subject Headings Pappas, study, Genes Influence Who Your Friends Are. This article incorporates text from the United States National Library of Medicine, which is in the public domain
27.
Dopamine transporter
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DAT is implicated in a number of dopamine-related disorders, including attention deficit hyperactivity disorder, bipolar disorder, clinical depression, and alcoholism. The gene that encodes the DAT protein is located on human chromosome 5, consists of 15 coding exons, DAT is an integral membrane protein that removes dopamine from the synaptic cleft and deposits it into surrounding cells, thus terminating the signal of the neurotransmitter. Dopamine underlies several aspects of cognition, including reward, and DAT facilitates regulation of that signal, DAT is a symporter that moves dopamine across the cell membrane by coupling the movement to the energetically-favorable movement of sodium ions moving from high to low concentration into the cell. DAT function requires the binding and co-transport of two Na+ ions and one Cl− ion with the dopamine substrate. The driving force for DAT-mediated dopamine reuptake is the ion concentration gradient generated by the plasma membrane Na+/K+ ATPase, in the most widely accepted model for monoamine transporter function, sodium ions must bind to the extracellular domain of the transporter before dopamine can bind. Once dopamine binds, the protein undergoes a change, which allows both sodium and dopamine to unbind on the intracellular side of the membrane. Chloride ions are also needed to prevent a buildup of positive charge and these studies have also shown that transport rate and direction is totally dependent on the sodium gradient. Because of the coupling of the membrane potential and the sodium gradient. In addition, the transporter may contribute to dopamine release when the neuron depolarizes, preliminary evidence suggests that the dopamine transporter couples to L-type voltage-gated calcium channels, which are expressed in virtually all dopamine neurons. The initial determination of the topology of DAT was based upon hydrophobic sequence analysis. These methods predicted twelve transmembrane domains with an extracellular loop between the third and fourth TMDs. The exact structure of the transporter was elucidated in 2013 by X-ray crystallography, regional distribution of DAT has been found in areas of the brain with established dopaminergic circuitry including, nigrostriatal, mesolimbic, and mesocortical pathways. The nuclei that make up these pathways have distinct patterns of expression, gene expression patterns in the adult mouse show high expression in the substantia nigra pars compacta. This pattern makes sense for a protein that regulates dopamine levels in the synapse, staining in the striatum and nucleus accumbens of the mesolimbic pathway was dense and heterogeneous. In the striatum, DAT is localized in the membrane of axon terminals. Double immunocytochemistry demonstrated DAT colocalization with two markers of nigrostriatal terminals, tyrosine hydroxylase and D2 dopamine receptors. The latter was thus demonstrated to be an autoreceptor on cells that release dopamine, surprisingly, DAT was not identified within any synaptic active zones. These results suggest that striatal dopamine reuptake may occur outside of synaptic specializations once dopamine diffuses from the synaptic cleft, in the substantia nigra, DAT is localized to axonal and dendritic plasma membranes
28.
Benocyclidine
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Benocyclidine, also known as benzothiophenylcyclohexylpiperidine, is a psychoactive recreational drug of the arylcyclohexylamine class which is related to phencyclidine. It was first described in a patent application naming Marc Caron and it acts as a potent and selective dopamine reuptake inhibitor and a psychostimulant. It has been used to label the dopamine transporter, BCP was also used to try to find a common pharmacophore for DRI type stimulants
29.
BDPC
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BDPC is a potent narcotic analgesic with a distinctive arylcyclohexylamine chemical structure. It was developed by Daniel Lednicer at Upjohn in the 1970s, initial studies estimated that it was around 10,000 times the strength of morphine in animal models. However, later assigned a value of 504 times the potency of morphine for the more active trans-isomer. To date, it is if this drug has been used by humans, however. C-8813 Cebranopadol Ciramadol Faxeladol Profadol Tapentadol Tramadol
30.
3-MeO-PCP
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3-Methoxyphencyclidine is a dissociative anesthetic drug that has been sold online as a designer drug. The compound was first synthesized in 1979 to investigate the structure-activity relationship of phencyclidine derivatives, the activity of 3-MeO-PCP in humans was not described until 1999 when a chemist using the pseudonym John Q. Beagle wrote that 3-MeO-PCP was qualitatively similar to PCP with comparable potency, 3-MeO-PCP binds to the NMDA receptor with higher affinity than PCP and has the highest affinity of the three isomeric anisyl-substitutions, followed by 2-MeO-PCP and 4-MeO-PCP. 3-MeO-PCP was preceded by the less potent dissociative 4-MeO-PCP and first became available as a chemical in 2011. Swedens public health agency suggested classifying 3-MeO-PCP as hazardous substance on November 10,2014, 3-MeO-PCP is banned in the Czech Republic. Arylcyclohexylamine Ketamine 3-HO-PCP 3-MeO-PCE 3-MeO-PCMo 4-MeO-PCP Methoxyketamine
31.
4-MeO-PCP
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4-Methoxyphencyclidine is a dissociative anesthetic drug that has been sold online as a research chemical. The synthesis of 4-MeO-PCP was first reported in 1965 by the Parke-Davis medicinal chemist Victor Maddox, a 1999 review published by a chemist using the pseudonym John Q. Users have reported differences in active dose, these discrepancies can be partially explained by the presence of unreacted PCC. Though 4-MeO-PCP has been suggested to possess dopaminergic activity, it is a selective ligand for the NMDA receptor without appreciable affinity for the dopamine transporter. Swedens public health agency suggested classifying 4-MeO-PCP as hazardous substance on November 10,2014, arylcyclohexylamine 3-HO-PCP 3-MeO-PCE 3-MeO-PCMo 3-MeO-PCP Methoxetamine Methoxyketamine
32.
Arketamine
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Arketamine, also -ketamine or --ketamine, is the - enantiomer of ketamine. On the other hand, it appears to be effective as an antidepressant. Relative to esketamine, arketamine possesses 4–5 times lower affinity for the PCP site of the NMDA receptor, in accordance, arketamine is significantly less potent than racemic ketamine and especially esketamine in terms of anesthetic, analgesic, and sedative-hypnotic effects. Esketamine inhibits the dopamine transporter about 8-fold more potently than does arketamine, arketamine and esketamine possess similar potency for interaction with the muscarinic acetylcholine receptors. Paradoxically, arketamine shows greater and longer-lasting rapid antidepressant effects in animal models of relative to esketamine. The picture is unclear however, and other mechanisms have also been implicated, as such, arketamine may have a lower propensity for producing psychotomimetic effects and a lower abuse potential in addition to superior antidepressant efficacy
33.
Esketamine
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Esketamine is a general anaesthetic and a dissociative. It is the S enantiomer of the drug ketamine, a general anaesthetic, esketamine acts primarily as a non-competitive N-methyl-D-aspartate receptor antagonist, but is also a dopamine reuptake inhibitor. As of August 18,2016, it is in phase III clinical trials for treatment-resistant depression, esketamine is approximately twice as potent as racemic ketamine. It is eliminated from the body more quickly than arketamine or racemic ketamine. A number of studies have suggested that esketamine has a more medically useful pharmacological action than arketamine or racemic ketamine, however a number of studies have suggested the contrary. Esketamine inhibits dopamine transporters eight times more than arketamine and this increases dopamine activity in the brain. At doses causing the same intensity of effects, esketamine is generally considered to be more pleasant by patients. Patients also generally recover mental function more quickly after being treated with pure esketamine and this is however in contradiction with R-ketamine being devoid of psychotomimetic side effects. Esketamine has an affinity for the PCP binding site of the NMDA receptor 3-4 times higher than that of arketamine, unlike arketamine, esketamine does not bind significantly to sigma receptors. Esketamine increases glucose metabolism in frontal cortex, while arketamine decreases glucose metabolism in the brain and this difference may be responsible for the fact that esketamine generally has a more dissociative or hallucinogenic effect while arketamine is reportedly more relaxing. However, another study found no difference between racemic and -ketamine on the level of vigilance. Interpretation of this finding is complicated by the fact that racemic ketamine comprises 50% -ketamine, a 2013 study in mice found that the rapid antidepressant effect of arketamine was greater and lasted longer than that of esketamine in mice
34.
Methoxyketamine
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Methoxyketamine or 2-MeO-2-deschloroketamine is a designer drug of the arylcyclohexylamine class first reported in 1963. It is an analog of ketamine in which the atom has been replaced with a methoxy group. Its synthesis by rearrangement of an amino ketone has been reported, as an arylcyclohexylamine, methoxyketamine most likely functions as an NMDA receptor antagonist. It may produce sedative, hallucinogenic, and anesthetic effects, 3-HO-PCP 3-MeO-PCE 3-MeO-PCP Methoxetamine Methoxydine N-Ethylnorketamine
