1.
Benzodiazepine
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Benzodiazepines, sometimes called benzos, are a class of psychoactive drugs whose core chemical structure is the fusion of a benzene ring and a diazepine ring. In 1977 benzodiazepines were globally the most prescribed medications, Benzodiazepines enhance the effect of the neurotransmitter gamma-aminobutyric acid at the GABAA receptor, resulting in sedative, hypnotic, anxiolytic, anticonvulsant, and muscle relaxant properties. High doses of many shorter-acting benzodiazepines may also cause anterograde amnesia and these properties make benzodiazepines useful in treating anxiety, insomnia, agitation, seizures, muscle spasms, alcohol withdrawal and as a premedication for medical or dental procedures. Benzodiazepines are categorized as either short-, intermediate-, or long-acting, short- and intermediate-acting benzodiazepines are preferred for the treatment of insomnia, longer-acting benzodiazepines are recommended for the treatment of anxiety. Benzodiazepines are generally viewed as safe and effective for use, although cognitive impairment. A minority of people can have paradoxical reactions such as worsened agitation or panic, long-term use is controversial because of concerns about adverse psychological and physical effects, decreasing effectiveness, and physical dependence and withdrawal. As a result of adverse effects associated with the use of benzodiazepines, withdrawal from benzodiazepines, in general. There is controversy concerning the safety of benzodiazepines in pregnancy, Benzodiazepines can be taken in overdoses and can cause dangerous deep unconsciousness. However, they are less toxic than their predecessors, the barbiturates, when combined with other central nervous system depressants such as ethanol and opioids, the potential for toxicity and fatal overdose increases. Benzodiazepines are commonly misused and taken in combination with other drugs of abuse, most are administered orally, however, they can also be given intravenously, intramuscularly, or rectally. In general, benzodiazepines are well-tolerated and are safe and effective drugs in the term for a wide range of conditions. Tolerance can develop to their effects and there is also a risk of dependence and these factors, combined with other possible secondary effects after prolonged use such as psychomotor, cognitive, or memory impairments, limit their long-term applicability. The effects of use or misuse include the tendency to cause or worsen cognitive deficits, depression. The College of Physicians and Surgeons of British Columbia recommends discontinuing the usage of benzodiazepines in those on opioids, because of their effectiveness, tolerability, and rapid onset of anxiolytic action, benzodiazepines are frequently used for the treatment of anxiety associated with panic disorder. However, there is disagreement among expert bodies regarding the use of benzodiazepines for panic disorder. APA states that there is insufficient evidence to recommend any of the established panic disorder treatments over another, one advantage of benzodiazepines is that they alleviate the anxiety symptoms much faster than antidepressants, and therefore may be preferred in patients for whom rapid symptom control is critical. However, this advantage is offset by the possibility of developing benzodiazepine dependence, APA does not recommend benzodiazepines for persons with depressive symptoms or a recent history of substance abuse. Although major concerns about benzodiazepine tolerance and withdrawal have been raised, for many such patients stable doses of benzodiazepines retain their efficacy over several years
2.
Hypnotic
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This group is related to sedatives. Whereas the term sedative describes drugs that serve to calm or relieve anxiety, because these two functions frequently overlap, and because drugs in this class generally produce dose-dependent effects they are often referred to collectively as sedative-hypnotic drugs. Hypnotic drugs are prescribed for insomnia and other sleep disorders. When prescribed, hypnotic medication should be used for the shortest period of time necessary, most hypnotics prescribed today are either benzodiazepines or nonbenzodiazepines. Among individuals with sleep disorders,13. 7% are taking or prescribed nonbenzodiazepines, while 10. 8% are taking benzodiazepines, early classes of drugs, such as barbiturates, have fallen out of use in most practices but are still prescribed for some patients. In children, prescribing hypnotics is not yet acceptable unless used to treat night terrors or somnambulism, falling outside of the above-mentioned categories, the neuro-hormone melatonin has a hypnotic function. Research about using medications to treat insomnia evolved throughout the last half of the 20th century, treatment for insomnia in psychiatry dates back to 1869 when chloral hydrate was first used as a soporific. Barbiturates emerged as the first class of drugs that emerged in the early 1900s, although the best drug family at the time they were dangerous in overdose. During the 1970s, quinazolinones and benzodiazepines were introduced as alternatives to replace barbiturates. Benzodiazepines are not without their drawbacks, substance dependence is possible, questions have been raised as to whether they disturb sleep architecture. Nonbenzodiazepines are the most recent development, although its clear that they are less toxic than their predecessors, barbiturates, comparative efficacy over benzodiazepines have not been established. Without longitudinal studies, it is hard to determine, however some psychiatrists recommend these drugs, other sleep remedies that may be considered sedative-hypnotics exist, psychiatrists will sometimes prescribe medicines off-label if they have sedating effects. Examples of these include mirtazapine, clonidine, quetiapine, and the over-the-counter sleep aid diphenhydramine, off-label sleep remedies are particularly useful when first-line treatment is unsuccessful or deemed unsafe. Barbiturates are drugs that act as central nervous system depressants, and can produce a wide spectrum of effects. They are also effective as anxiolytics, hypnotics, and anticonvulsants, barbiturates also have analgesic effects, however, these effects are somewhat weak, preventing barbiturates from being used in surgery in the absence of other analgesics. They have dependence liability, both physical and psychological, however, barbiturates are still used in general anesthesia, for epilepsy, and assisted suicide. Barbiturates are derivatives of barbituric acid, the principal mechanism of action of barbiturates is believed to be positive allosteric modulation of GABAA receptors. Examples include amobarbital, pentobarbital, phenobarbital, secobarbital, and sodium thiopental, quinazolinones are also a class of drugs which function as hypnotic/sedatives that contain a 4-quinazolinone core
3.
Heterocyclic compound
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A heterocyclic compound or ring structure is a cyclic compound that has atoms of at least two different elements as members of its ring. Heterocyclic chemistry is the branch of chemistry dealing with the synthesis, properties. Examples of heterocyclic compounds include all of the acids, the majority of drugs, most biomass. Although heterocyclic compounds may be inorganic, most contain at least one carbon, while atoms that are neither carbon nor hydrogen are normally referred to in organic chemistry as heteroatoms, this is usually in comparison to the all-carbon backbone. But this does not prevent a compound such as borazine from being labelled heterocyclic, IUPAC recommends the Hantzsch-Widman nomenclature for naming heterocyclic compounds. Heterocyclic compounds can be classified based on their electronic structure. The saturated heterocycles behave like the acyclic derivatives, thus, piperidine and tetrahydrofuran are conventional amines and ethers, with modified steric profiles. Therefore, the study of heterocyclic chemistry focuses especially on unsaturated derivatives, included are pyridine, thiophene, pyrrole, and furan. Another large class of heterocycles are fused to rings, which for pyridine, thiophene, pyrrole, and furan are quinoline, benzothiophene, indole. Fusion of two benzene rings gives rise to a large family of compounds, respectively the acridine, dibenzothiophene, carbazole. The unsaturated rings can be classified according to the participation of the heteroatom in the pi system, heterocycles with three atoms in the ring are more reactive because of ring strain. Those containing one heteroatom are, in general, stable and those with two heteroatoms are more likely to occur as reactive intermediates. Five-membered rings with one heteroatom, The 5-membered ring compounds containing two heteroatoms, at least one of which is nitrogen, are called the azoles. Thiazoles and isothiazoles contain a sulfur and an atom in the ring. A large group of 5-membered ring compounds with three heteroatoms also exists, one example is dithiazoles that contain two sulfur and a nitrogen atom. Five-member ring compounds with four heteroatoms, With 5-heteroatoms, the compound may be considered rather than heterocyclic. With 7-membered rings, the heteroatom must be able to provide an empty pi orbital for normal aromatic stabilization to be available, otherwise, for example, with the benzo-fused unsaturated nitrogen heterocycles, pyrrole provides indole or isoindole depending on the orientation. The pyridine analog is quinoline or isoquinoline, for azepine, benzazepine is the preferred name
4.
Zopiclone
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Zopiclone is a nonbenzodiazepine hypnotic agent used in the treatment of insomnia. It is a cyclopyrrolone, which increases the transmission of the neurotransmitter gamma-Aminobutyric acid in the central nervous system, as benzodiazepines do. As zopiclone is sedating, it is marketed as a sleeping pill and it works by causing a depression or tranquilization of the central nervous system. After prolonged use, the body can become accustomed to the effects of zopiclone, when the dose is then reduced or the drug is abruptly stopped, withdrawal symptoms may result. These can include a range of similar to those of benzodiazepine withdrawal. In the United States, zopiclone is not commercially available, although its active stereoisomer, Zopiclone is a controlled substance in the United States, Japan, Brazil, and some European countries, and may be illegal to possess without a prescription. Zopiclone is known colloquially as a Z-drug, other Z-drugs include zaleplon and zolpidem and were initially thought to be less addictive or habit-forming than benzodiazepines. However, this appraisal has shifted somewhat in the last few years as cases of addiction and habituation have been presented, Zopiclone is recommended to be taken on a short-term basis, usually a week or less. Daily or continuous use of the drug is not usually advised, Zopiclone is indicated for the short-term treatment of insomnia where sleep initiation or sleep maintenance are prominent symptoms. Long-term use is not recommended, as tolerance, dependence, Zopiclone is ineffective in increasing daytime sleep time in shift workers. Zopiclone, similar to benzodiazepines and nonbenzodiazepine hypnotic drugs, causes impairments in body balance. Falls and hip fractures are frequently reported, the combination with alcohol consumption increases these impairments. Partial, but incomplete tolerance develops to these impairments, compared with the benzodiazepines, the nonbenzodiazepine sedative-hypnotics, such as zopiclone, offer few if any advantages in efficacy or tolerability in elderly persons. Newer agents such as the Melatonin receptor agonists may be more suitable, in addition, the effectiveness and safety of long-term use of nonbenzodiazepine hypnotic drugs remains to be determined. Zopiclone causes impaired driving skills similar to those of benzodiazepines, patients who drive motor vehicles should not take zopiclone unless they stop driving due to a significant increased risk of accidents in zopiclone users. Zopiclone induces impairment of psychomotor function, driving or operating machinery should be avoided after taking zopiclone as effects can carry over to the next day, including impaired hand eye coordination. Alcohol should be avoided when using zopiclone, as alcohol and zopiclone enhance the effects of each other, patients with liver disease eliminate zopiclone much more slowly than normal patients and in addition experience exaggerated pharmacological effects of the drug. Zopiclone increases sway and increases the number of falls in older people, falls are a significant cause of death in older people
5.
Skeletal formula
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A skeletal formula shows the skeletal structure or skeleton of a molecule, which is composed of the skeletal atoms that make up the molecule. It is represented in two dimensions, as on a page of paper and it employs certain conventions to represent carbon and hydrogen atoms, which are the most common in organic chemistry. The technique was developed by the organic chemist Friedrich August Kekulé von Stradonitz, Skeletal formulae have become ubiquitous in organic chemistry, partly because they are relatively quick and simple to draw. As in a Lewis structure, a doubled or tripled line segment indicates double or triple bonding, the skeletal structure of an organic compound is the series of atoms bonded together that form the essential structure of the compound. The skeleton can consist of chains, branches and/or rings of bonded atoms, Skeletal atoms other than carbon or hydrogen are called heteroatoms. The skeleton has hydrogen and/or various substituents bonded to its atoms, hydrogen is the most common non-carbon atom that is bonded to carbon and, for simplicity, is not explicitly drawn. For example, in the image below, the formula of hexane is shown. The carbon atom labeled C1 appears to have one bond. The carbon atom labelled C3 has two bonds to other carbons and is bonded to two hydrogen atoms as well. NOTE, It doesnt matter which end of the chain you start numbering from, the condensed formula or the IUPAC name will confirm the orientation. Some molecules will become familiar regardless of the orientation, any hydrogen atoms bonded to non-carbon atoms are drawn explicitly. In ethanol, C2H5OH, for instance, the hydrogen bonded to oxygen is denoted by the symbol H. Lines representing heteroatom-hydrogen bonds are usually omitted for clarity and compactness and these bonds are sometimes drawn out in full in order to accentuate their presence when they participate in reaction mechanisms. Shown below for comparison are a model of the actual three-dimensional structure of the ethanol molecule in the gas phase, the Lewis structure. All atoms that are not carbon or hydrogen are signified by their symbol, for instance Cl for chlorine, O for oxygen, Na for sodium. These atoms are known as heteroatoms in the context of organic chemistry. There are also symbols that appear to be chemical element symbols and these are known as pseudoelement symbols or organic elements. The most widely used symbol is Ph, which represents the phenyl group, boc for the t-butoxycarbonyl group Cbz or Z for the carboxybenzyl group Fmoc for the fluorenylmethoxycarbonyl group Two atoms can be bonded by sharing more than one pair of electrons
6.
GABAA receptor
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The GABAA receptor is an ionotropic receptor and ligand-gated ion channel. Its endogenous ligand is γ-aminobutyric acid, the major inhibitory neurotransmitter in the nervous system. Upon activation, the GABAA receptor selectively conducts Cl− through its pore and this causes an inhibitory effect on neurotransmission by diminishing the chance of a successful action potential occurring. The reversal potential of the GABAA-mediated IPSP in normal solution is −70 mV, the active site of the GABAA receptor is the binding site for GABA and several drugs such as muscimol, gaboxadol, and bicuculline. The protein also contains a number of different allosteric binding sites which modulate the activity of the receptor indirectly, GABAA receptors occur in all organisms that have a nervous system. To a limited extent the receptors can be found in non-neuronal tissues, due to their wide distribution within the nervous system of mammals they play a role in virtually all brain functions. The ionotropic GABAA receptor protein complex is also the target of the benzodiazepine class of tranquilizer drugs. In addition peripheral benzodiazepine receptors exist which are not associated with GABAA receptors, in order for GABAA receptors to be sensitive to the action of benzodiazepines they need to contain an α and a γ subunit, between which the benzodiazepine binds. This potentiates the effect of the available GABA leading to sedative. Different benzodiazepines have different affinities for GABAA receptors made up of different collection of subunits, the much sought structure of GABAA receptor was finally resolved, with the disclosure of the crystal structure of human β3 homopentameric GABAA receptor. GABAA receptor is a transmembrane receptor that consists of five subunits arranged around a central pore. Each subunit comprises four transmembrane domains with both the N- and C-terminus located extracellularly, the receptor sits in the membrane of its neuron, usually localized at a synapse, postsynaptically. However, some isoforms may be found extrasynaptically, the net effect is typically inhibitory, reducing the activity of the neuron. The GABAA channel opens quickly and thus contributes to the part of the inhibitory post-synaptic potential. The endogenous ligand that binds to the site is inosine. There are numerous subunit isoforms for the GABAA receptor, which determine the receptors agonist affinity, chance of opening, conductance, five subunits can combine in different ways to form GABAA channels. The minimal requirement to produce a GABA-gated ion channel is the inclusion of both α and β subunits, but the most common type in the brain is a pentamer comprising two αs, two βs, and a γ. The receptor binds two GABA molecules, at the interface between an α and a β subunit, a number of ligands have been found to bind to various sites on the GABAA receptor complex and modulate it besides GABA itself
7.
Pagoclone
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Pagoclone is an anxiolytic agent from the cyclopyrrolone family, related to better-known drugs such as the sleeping medication zopiclone. It binds with roughly equivalent high affinity to the binding site of human GABAA receptors containing either an α1, α2. It is a partial agonist at α1-, α2- and α5-containing GABAA receptors, in rats 5′-hydroxypagoclone was identified as a major metabolite. This metabolite has a greater efficacy at the α1 subtype than the parent compound and was shown to have significant anxiolytic-like activity. In contrast to zopiclone, pagoclone produces anxiolytic effects with little sedative or amnestic actions at low doses and its effect can be quickly reversed by the action of flumazenil, which is already used as an antidote to benzodiazepine overdose. Nutt has published studies praising the potential of pagoclone which were financed by Indevus which was seeking funding for a production of the compound. The long-term safety of pagoclone has not been assessed, pagoclone was trialed as a drug to improve a stammerers speech fluency, but research for this application was discontinued following disappointing results in Phase II clinical trials. Pagoclone and pazinaclone are both isoindolone Reaction of 2-Amino-7-chloro-1, 8-naphthyridine with phthalic anhydride leads to the corresponding phthalimide, selective reduction of one of the imide carbonyl groups give the corresponding alcohol
8.
Pazinaclone
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Pazinaclone is a sedative and anxiolytic drug in the cyclopyrrolone family of drugs. Some other cyclopyrrolone drugs include zopiclone and eszopiclone, pazinaclone produces its sedative and anxiolytic effects by acting as a partial agonist at GABAA benzodiazepine receptors, although pazinaclone is more subtype-selective than most benzodiazepines. Reaction of 2-amino-7-chloro-1, 8-naphthyridine with phthalic anhydride leads to the corresponding phthalimide, selective reduction of one of the imide carbonyl groups in essence converts that to an aldehyde. Condensation with tert-butylacetate gives the Wittig product
9.
Neurotransmitter
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Neurotransmitters, also known as chemical messengers, are endogenous chemicals that enable neurotransmission. They transmit signals across a synapse, such as a neuromuscular junction, from one neuron to another target neuron, muscle cell. Neurotransmitters are released from synaptic vesicles in synapses into the synaptic cleft, neurotransmitters play a major role in shaping everyday life and functions. Their exact numbers are unknown, but more than 100 chemical messengers have been uniquely identified, neurotransmitters are stored in a synapse in synaptic vesicles, clustered beneath the membrane in the axon terminal located at the presynaptic side of the synapse. Neurotransmitters are released into and diffused across the cleft, where they bind to specific receptors in the membrane on the postsynaptic side of the synapse. Most neurotransmitters are about the size of an amino acid, however. Nevertheless, short-term exposure of the receptor to a neurotransmitter is typically sufficient for causing a postsynaptic response by way of synaptic transmission, in response to a threshold action potential or graded electrical potential, a neurotransmitter is released at the presynaptic terminal. Low level baseline release also occurs without electrical stimulation, the released neurotransmitter may then move across the synapse to be detected by and bind with receptors in the postsynaptic neuron. Binding of neurotransmitters may influence the postsynaptic neuron in either an inhibitory or excitatory way and this neuron may be connected to many more neurons, and if the total of excitatory influences are greater than those of inhibitory influences, the neuron will also fire. Ultimately it will create a new action potential at its axon hillock to release neurotransmitters, until the early 20th century, scientists assumed that the majority of synaptic communication in the brain was electrical. However, through the careful histological examinations by Ramón y Cajal, upon completion of this experiment, Loewi asserted that sympathetic regulation of cardiac function can be mediated through changes in chemical concentrations. Furthermore, Otto Loewi is credited with discovering acetylcholine —the first known neurotransmitter, some neurons do, however, communicate via electrical synapses through the use of gap junctions, which allow specific ions to pass directly from one cell to another. There are four criteria for identifying neurotransmitters, The chemical must be synthesized in the neuron or otherwise be present in it. When the neuron is active, the chemical must be released, the same response must be obtained when the chemical is experimentally placed on the target. A mechanism must exist for removing the chemical from its site of activation after its work is done, have little or no effect on membrane voltage, but have a common carrying function such as changing the structure of the synapse. Communicate by sending messages that affect the release or reuptake of transmitters. Various techniques and experiments such as staining, stimulating, and collecting can be used to identify throughout the central nervous system. There are many different ways to classify neurotransmitters, dividing them into amino acids, peptides, and monoamines is sufficient for some classification purposes
