Intrinsic activity or efficacy refers to the relative ability of a drug-receptor complex to produce a maximum functional response. This must be distinguished from the affinity, a measure of the ability of the drug to bind to its molecular target, the EC50, a measure of the potency of the drug and, proportional to both efficacy and affinity; this use of the word "efficacy" was introduced by Stephenson to describe the way in which agonists vary in the response they produce when they occupy the same number of receptors. High efficacy agonists can produce the maximal response of the receptor system while occupying a low proportion of the receptors in that system. Agonists of lower efficacy are not as efficient at producing a response from the drug-bound receptor, by stabilizing the active form of the drug-bound receptor. Therefore, they may not be able to produce the same maximal response when they occupy the entire receptor population, as the efficiency of transformation of the inactive form of the drug-receptor complex to the active drug-receptor complex may not be high enough to evoke a maximal response.
Since the observed response may be less than maximal in systems with no spare receptor reserve, some low efficacy agonists are referred to as partial agonists. However, it is worth bearing in mind that these terms are relative - partial agonists may appear as full agonists in a different system/experimental setup, as when the number of receptors increases, there may be enough drug-receptor complexes for a maximum response to be produced with individually low efficacy of transducing the response. There are relatively few true full agonists or silent antagonists. Many antagonists are in fact partial agonists or inverse agonists, but with low efficacy. Compounds considered. Another case is represented by silent agonists, which are ligands that can place a receptor an ion channel, into a desensitized state with little or no apparent activation of it, forming a complex that can subsequently generate currents when treated with an allosteric modulator. There is a distinction between intrinsic activity.
Efficacy has been treated as a proportionality constant between the binding of the drug and the generation of the biological response. Stephenson defined efficacy as: S = e p where p is the proportion of agonist-bound receptors and S is the stimulus to the biological system; the response is generated by an unknown function f, assumed to be hyperbolic. This model was arguably flawed in that it did not incorporate the equilibrium between the inactivated agonist-bound-receptor and the activated agonist-bound-receptor, shown in the del Castillo Katz model. Furchgott improved on Stephenson's model with the definition of efficacy, e, as S = ε T o t ⏟ e ⋅ p where ε is the intrinsic efficacy and T o t is the total concentration of receptors; these models of efficacy have been criticised and many more. The models of efficacy are shown in. Intrinsic activity of a test agonist is defined as: I A = maximal response to the test agonist maximal response to full agonist
Cocaine known as coke, is a strong stimulant used as a recreational drug. It is snorted, inhaled as smoke, or dissolved and injected into a vein. Mental effects may include loss of contact with reality, an intense feeling of happiness, or agitation. Physical symptoms may include a fast heart rate and large pupils. High doses can result in high blood pressure or body temperature. Effects begin within seconds to last between five and ninety minutes. Cocaine has a small number of accepted medical uses such as numbing and decreasing bleeding during nasal surgery. Cocaine is addictive due to its effect on the reward pathway in the brain. After a short period of use, there is a high risk, its use increases the risk of stroke, myocardial infarction, lung problems in those who smoke it, blood infections, sudden cardiac death. Cocaine sold on the street is mixed with local anesthetics, quinine, or sugar, which can result in additional toxicity. Following repeated doses a person may have decreased ability to feel pleasure and be physically tired.
Cocaine acts by inhibiting the reuptake of serotonin and dopamine. This results in greater concentrations of these three neurotransmitters in the brain, it can cross the blood–brain barrier and may lead to the breakdown of the barrier. Cocaine is a occurring substance found in the coca plant, grown in South America. In 2013, 419 kilograms were produced legally, it is estimated. With further processing crack cocaine can be produced from cocaine. Cocaine is the second most used illegal drug globally, after cannabis. Between 14 and 21 million people use the drug each year. Use is highest in North America followed by South America. Between one and three percent of people in the developed world have used cocaine at some point in their life. In 2013, cocaine use directly resulted in 4,300 deaths, up from 2,400 in 1990; the leaves of the coca plant have been used by Peruvians since ancient times. Cocaine was first isolated from the leaves in 1860. Since 1961, the international Single Convention on Narcotic Drugs has required countries to make recreational use of cocaine a crime.
Topical cocaine can be used as a local numbing agent to help with painful procedures in the mouth or nose. Cocaine is now predominantly used for lacrimal duct surgery; the major disadvantages of this use are cocaine's potential for cardiovascular toxicity and pupil dilation. Medicinal use of cocaine has decreased as other synthetic local anesthetics such as benzocaine, proparacaine and tetracaine are now used more often. If vasoconstriction is desired for a procedure, the anesthetic is combined with a vasoconstrictor such as phenylephrine or epinephrine; some ENT specialists use cocaine within the practice when performing procedures such as nasal cauterization. In this scenario dissolved cocaine is soaked into a ball of cotton wool, placed in the nostril for the 10–15 minutes before the procedure, thus performing the dual role of both numbing the area to be cauterized, vasoconstriction; when used this way, some of the used cocaine may be absorbed through oral or nasal mucosa and give systemic effects.
An alternative method of administration for ENT surgery is mixed with adrenaline and sodium bicarbonate, as Moffett's solution. Cocaine is a powerful nervous system stimulant, its effects can last from 30 minutes to an hour. The duration of cocaine's effects depends on the route of administration. Cocaine can be in the form of fine white powder, bitter to the taste; when inhaled or injected, it causes a numbing effect. Crack cocaine is a smokeable form of cocaine made into small "rocks" by processing cocaine with sodium bicarbonate and water. Crack cocaine is referred to. Cocaine use leads to increases in alertness, feelings of well-being and euphoria, increased energy and motor activity, increased feelings of competence and sexuality. Coca leaves are mixed with an alkaline substance and chewed into a wad, retained in the mouth between gum and cheek and sucked of its juices; the juices are absorbed by the mucous membrane of the inner cheek and by the gastrointestinal tract when swallowed. Alternatively, coca leaves can be consumed like tea.
Ingesting coca leaves is an inefficient means of administering cocaine. Because cocaine is hydrolyzed and rendered inactive in the acidic stomach, it is not absorbed when ingested alone. Only when mixed with a alkaline substance can it be absorbed into the bloodstream through the stomach; the efficiency of absorption of orally administered cocaine is limited by two additional factors. First, the drug is catabolized by the liver. Second, capillaries in the mouth and esophagus constrict after contact with the drug, reducing the surface area over which the drug can be absorbed. Cocaine metabolites can be detected in the urine of subjects that have sipped one cup of coca leaf infusion. Orally administered cocaine takes 30 minutes to enter the bloodstream. Only a third of an oral dose is absorbed, although absorption has been shown to reach 60% in controlled settings. Given the slow rate of absorption, maximum physiological and psychotropic effects are attained 60 minutes after cocaine is administered by ingestion.
While the onset of these effects is slow, the effects are sustained for approxima
The Jmol applet, among other abilities, offers an alternative to the Chime plug-in, no longer under active development. While Jmol has many features that Chime lacks, it does not claim to reproduce all Chime functions, most notably, the Sculpt mode. Chime requires plug-in installation and Internet Explorer 6.0 or Firefox 2.0 on Microsoft Windows, or Netscape Communicator 4.8 on Mac OS 9. Jmol operates on a wide variety of platforms. For example, Jmol is functional in Mozilla Firefox, Internet Explorer, Google Chrome, Safari. Chemistry Development Kit Comparison of software for molecular mechanics modeling Jmol extension for MediaWiki List of molecular graphics systems Molecular graphics Molecule editor Proteopedia PyMOL SAMSON Official website Wiki with listings of websites and moodles Willighagen, Egon. "Fast and Scriptable Molecular Graphics in Web Browsers without Java3D". Doi:10.1038/npre.2007.50.1
In vitro studies are performed with microorganisms, cells, or biological molecules outside their normal biological context. Colloquially called "test-tube experiments", these studies in biology and its subdisciplines are traditionally done in labware such as test tubes, Petri dishes, microtiter plates. Studies conducted using components of an organism that have been isolated from their usual biological surroundings permit a more detailed or more convenient analysis than can be done with whole organisms. In contrast to in vitro experiments, in vivo studies are those conducted in animals, including humans, whole plants. In vitro studies are conducted using components of an organism that have been isolated from their usual biological surroundings, such as microorganisms, cells, or biological molecules. For example, microorganisms or cells can be studied in artificial culture media, proteins can be examined in solutions. Colloquially called "test-tube experiments", these studies in biology and their subdisciplines are traditionally done in test tubes, Petri dishes, etc.
They now involve the full range such as the omics. In contrast, studies conducted in living beings are called in vivo. Examples of in vitro studies include: the isolation and identification of cells derived from multicellular organisms in. Viruses, which only replicate in living cells, are studied in the laboratory in cell or tissue culture, many animal virologists refer to such work as being in vitro to distinguish it from in vivo work in whole animals. Polymerase chain reaction is a method for selective replication of specific DNA and RNA sequences in the test tube. Protein purification involves the isolation of a specific protein of interest from a complex mixture of proteins obtained from homogenized cells or tissues. In vitro fertilization is used to allow spermatozoa to fertilize eggs in a culture dish before implanting the resulting embryo or embryos into the uterus of the prospective mother. In vitro diagnostics refers to a wide range of medical and veterinary laboratory tests that are used to diagnose diseases and monitor the clinical status of patients using samples of blood, cells, or other tissues obtained from a patient.
In vitro testing has been used to characterize specific adsorption, distribution and excretion processes of drugs or general chemicals inside a living organism. These ADME process parameters can be integrated into so called "physiologically based pharmacokinetic models" or PBPK. In vitro studies permit a species-specific, more convenient, more detailed analysis than can be done with the whole organism. Just as studies in whole animals more and more replace human trials, so are in vitro studies replacing studies in whole animals. Living organisms are complex functional systems that are made up of, at a minimum, many tens of thousands of genes, protein molecules, RNA molecules, small organic compounds, inorganic ions, complexes in an environment, spatially organized by membranes, in the case of multicellular organisms, organ systems; these myriad components interact with each other and with their environment in a way that processes food, removes waste, moves components to the correct location, is responsive to signalling molecules, other organisms, sound, taste and balance.
This complexity makes it difficult to identify the interactions between individual components and to explore their basic biological functions. In vitro work simplifies the system under study, so the investigator can focus on a small number of components. For example, the identity of proteins of the immune system, the mechanism by which they recognize and bind to foreign antigens would remain obscure if not for the extensive use of in vitro work to isolate the proteins, identify the cells and genes that produce them, study the physical properties of their interaction with antigens, identify how those interactions lead to cellular signals that activate other components of the immune system. Another advantage of in vitro methods is that human cells can be studied without "extrapolation" from an experimental animal's cellular response. In vitro methods can be miniaturized and automated, yielding high-throughput screening methods for testing molecules in pharmacology or toxicology The primary disadvantage of in vitro experimental studies is that it may be challenging to extrapolate from the results of in vitro work back to the biology of the intact organism.
Investigators doing in vitro work must be careful to avoid over-interpretation of their results, which can lead to erroneous conclusions about organismal and systems biology. For example, scientists developing a new viral drug to treat an infection with a pathogenic virus may find that a candidate drug functions to prevent viral repl
Psychedelics are a class of drug whose primary action is to trigger psychedelic experiences via serotonin receptor agonism, causing thought and visual/auditory changes, altered state of consciousness. Major psychedelic drugs include mescaline, LSD, DMT. Studies show that psychedelics do not lead to addiction. Studies conducted using psilocybin in a psychotheraputic setting reveal that psychedelic drugs may assist with treating alcohol and nicotine addiction. Differing with other psychoactive drugs, such as stimulants and opioids, psychedelics tend to qualitatively alter ordinary conscious experience. Whereas stimulants cause energized feelings and opioids produce a relaxed euphoric state, the psychedelic experience is compared to non-ordinary forms of consciousness such as trance, yoga, religious ecstasy and near-death experiences. Most psychedelic drugs fall into one of the three families of chemical compounds: tryptamines, phenethylamines, or lysergamides. Although lysergamides are their own group they are a tryptamine.
Many psychedelic drugs are illegal worldwide under the UN conventions excepting use in a religious or research context. Despite these controls, recreational use of psychedelics is common; the term psychedelic is derived from the Greek words ψυχή and δηλείν, hence "soul-manifesting", the implication being that psychedelics can access the soul and develop unused potentials of the human mind. The word was coined in 1956 by British psychiatrist, Humphry Osmond, the spelling loathed by American ethnobotanist, Richard Schultes, but championed by the American psychologist, Timothy Leary. Aldous Huxley had suggested to Humphry Osmond in 1956 his own coinage phanerothyme; the term entheogenic has come into use to denote the use of psychedelic drugs in a religious/spiritual/mystical context. Psychedelics have a long history of traditional use in medicine and religion, for their perceived ability to promote physical and mental healing. In this context, they are known as entheogens. Native American practitioners using mescaline-containing cacti have reported success against alcoholism, Mazatec practitioners use psilocybin mushrooms for divination and healing.
Ayahuasca, which contains the potent psychedelic DMT, is used in Peru and other parts of South America for spiritual and physical healing as well as in religious festivals. Classical or serotonergic psychedelics include LSD, mescaline, DMT; this class of psychedelics includes the classical hallucinogens, including the lysergamides like LSD and LSA, tryptamines like psilocybin and DMT, phenethylamines like mescaline and 2C-B. Many of these psychedelics cause remarkably similar effects, despite their different chemical structure. However, many users report that the three families have subjectively different qualities in the "feel" of the experience, which are difficult to describe. At lower doses, these include sensory alterations, such as the warping of surfaces, shape suggestibility, color variations. Users report intense colors that they have not experienced, repetitive geometric shapes are common. Higher doses cause intense and fundamental alterations of sensory perception, such as synesthesia or the experience of additional spatial or temporal dimensions.
Some compounds, such as 2C-B, have tight "dose curves", meaning the difference between a non-event and an overwhelming disconnection from reality can be slight. There can be substantial differences between the drugs, however. For instance, 5-MeO-DMT produces the visual effects typical of other psychedelics and ibogaine is an NMDA receptor antagonist and κ-opioid receptor agonist in addition to being an agonist for the 5-HT2A receptors, resulting in dissociative effects as well. Research published in journal Cell Reports states that psychedelic drugs promote neural plasticity in rats and flies; the empathogen-entactogens are phenethylamines of the MDxx class such as MDMA, MDEA, MDA. Their effects are characterized by feelings of openness, empathy, heightened self-awareness, by mild audio and visual distortions, their adoption by the rave subculture is due to the enhancement of the overall social and musical experience. MDA is atypical to this experience causing hallucinations and psychedelic effects in equal profundity to the chemicals in the 5-HT2A agonist category, but with less mental involvement, is both a serotonin releaser and 5-HT2A receptor agonist.
Certain dissociative drugs acting via NMDA antagonism are known to produce what some might consider psychedelic effects. The main differences between dissociative psychedelics and serotonergic hallucinogens are that the dissociatives cause more intense derealization and depersonalization. For example, ketamine produces sensations of being disconnected from one's body and that the surrounding environment is unreal, as well as perceptual alterations seen with other psychedelics. Salvia divinorum is a dissociative, sometimes classified as an atypical psychedelic; the active molecule in the plant, salvinorin A, is a kappa opioid receptor agonist, working on a part of the brain that de
The rhesus macaque is one of the best-known species of Old World monkeys. It is listed as Least Concern in the IUCN Red List of Threatened Species in view of its wide distribution, presumed large population, its tolerance of a broad range of habitats. Native to South and Southeast Asia, rhesus macaque have the widest geographic ranges of any nonhuman primate, occupying a great diversity of altitudes and a great variety of habitats, from grasslands to arid and forested areas, but close to human settlements; the rhesus macaque is brown or grey in color and has a pink face, bereft of fur. Its tail is of medium length and averages between 22.9 cm. Adult males weigh about 7.7 kg. Females are smaller, averaging 5.3 kg in weight. Rhesus macaques have, on average, their ratio of arm length to leg length is 89%. They have a wide rib cage; the rhesus macaque has 32 teeth with a dental formula of bilophodont molars. The upper molars have four cusps: paracone, metacone and hypocone; the lower molars have four cusps: metaconid, protoconid and entoconid.
Rhesus macaques are native to India, Pakistan, Burma, Afghanistan, southern China, some neighboring areas. They have the widest geographic ranges of any nonhuman primate, occupying a great diversity of altitudes throughout Central and Southeast Asia. Inhabiting arid, open areas, rhesus macaques may be found in grasslands, in mountainous regions up to 2,500 m in elevation, they are regular swimmers. Babies as young as a few days old can swim, adults are known to swim over a half mile between islands, but are found drowned in small groups where their drinking waters lie. Rhesus macaques are noted for their tendency to move from rural to urban areas, coming to rely on handouts or refuse from humans, they adapt well to human presence, form larger troops in human-dominated landscapes than in forests. The southern and the northern distributional limits for rhesus and bonnet macaques currently run parallel to each other in the western part of India, are separated by a large gap in the center, converge on the eastern coast of the peninsula to form a distribution overlap zone.
This overlap region is characterized by the presence of mixed-species troops, with pure troops of both species sometimes occurring in close proximity to one another. The range extension of rhesus macaque – a natural process in some areas, a direct consequence of introduction by humans in other regions – poses grave implications for the endemic and declining populations of bonnet macaques in southern India; the Thai population is locally classified as endangered. There are about 1,000 troops at Wat Tham Pha Mak Ho, Tambon Si Songkhram, Wang Saphung district, Loei province; the name "rhesus" is reminiscent of the mythological king Rhesus of Thrace, a minor character in the Iliad. However, the French naturalist Jean-Baptiste Audebert, who applied the name to the species, stated: "it has no meaning". According to Zimmermann’s first description of 1780, the rhesus macaque is distributed in eastern Afghanistan, Bhutan, as far east as the Brahmaputra Valley in peninsular India and northern Pakistan.
Today, this is known as the Indian rhesus macaque M. m. mulatta, which includes the morphologically similar M. rhesus villosus, described by True in 1894, from Kashmir, M. m. mcmahoni, described by Pocock in 1932 from Kootai, Pakistan. Several Chinese subspecies of rhesus macaques were described between 1867 and 1917; the molecular differences identified among populations, are alone not consistent enough to conclusively define any subspecies. The Chinese subspecies can be divided as follows: M. m. mulatta is found in western and central China, in the south of Yunnan, southwest of Guangxi. M. m. tcheliensis, the north Chinese rhesus macaque, lives in the north of Henan, south of Shanxi, near Beijing. Some consider it as the most endangered subspecies. Others consider it synonymous with M. m. sanctijohannis, if not with M. m. mulatta. M. m. vestita, the Tibetan rhesus macaque, lives in the southeast of Tibet, northwest of Yunnan, including Yushu. M. m. littoralis, the south Chinese rhesus macaque, lives in Fujian, Anhui, Hunan, Guizhou, northwest of Guangdong, north of Guangxi, northeast of Yunnan, east of Sichuan, south of Shaanxi.
M. m. brevicaudus referred to as Pithecus brevicaudus, lives on the Hainan Island and Wanshan Islands in Guangdong, the islands near Hong Kong. M. m. siamica, the Indochinese rhesus macaque, is distributed in Myanmar, in the north of Thailand and Vietnam, in Laos, in the Chinese provinces of Anhui, northwest Guangxi, Hubei, Hunan and eastern Sichuan, western and south-central Yunnan. Around the spring of 1938, a colony of rhesus macaques called "the Nazuris" was released in and around Silver Springs in Florida by a tour boat operator known locally as "Colonel Tooey" to enhance his "Jungle C
In medicine, a side effect is an effect, whether therapeutic or adverse, secondary to the one intended. Developing drugs is a complicated process, because no two people are the same, so drugs that have no side effects, might be difficult for some people, it is difficult to make a drug that targets one part of the body but that doesn’t affect other parts, the fact that increases the risk of side effects in the untargeted parts. Drugs are prescribed or procedures performed for their side effects. For instance, X-rays were used as an imaging technique; the probability or chance of experiencing side effects are characterised as: Very common, ≥ 1⁄10 Common, 1⁄10 to 1⁄100 Uncommon, 1⁄100 to 1⁄1000 Rare, 1⁄1000 to 1⁄10000 Very rare, < 1⁄10000 Bevacizumab, used to slow the growth of blood vessels, has been used against dry age-related macular degeneration, as well as macular edema from diseases such as diabetic retinopathy and central retinal vein occlusion. Buprenorphine has been shown experimentally to be effective against refractory depression.
Bupropion, an anti-depressant, is used as a smoking cessation aid. In Ontario, smoking cessation drugs are not covered by provincial drug plans. Therefore, some physicians prescribe Wellbutrin for both indications. Carbamazepine is an approved treatment for bipolar disorder and epileptic seizures, but it has side effects useful in treating attention-deficit hyperactivity disorder, phantom limb syndrome, paroxysmal extreme pain disorder and post-traumatic stress disorder. Dexamethasone and betamethasone in premature labor, to enhance pulmonary maturation of the fetus. Doxepin has been used to treat angiodema and severe allergic reactions due to its strong antihistamine properties. Gabapentin, approved for treatment of seizures and postherpetic neuralgia in adults, has side-effects which are useful in treating bipolar disorder1, essential tremor, hot flashes, migraine prophylaxis, neuropathic pain syndromes, phantom limb syndrome, restless leg syndrome. Hydroxyzine, an antihistamine, is used as an anxiolytic.
Magnesium sulfate in obstetrics for premature preeclampsia. Methotrexate, approved for the treatment of choriocarcinoma, is used for the medical treatment of an unruptured ectopic pregnancy; the SSRI medication sertraline is approved as an antidepressant but delays conjugal climax in men, thus may be supplied to those in which climax is premature. Sildenafil was intended for pulmonary hypertension. Terazosin, an α1-adrenergic antagonist approved to treat benign prostatic hyperplasia and hypertension, is used off-label to treat drug induced diaphoresis and hyperhidrosis. Echinacea – more than 20 different types of reactions have been reported, including asthma attacks, loss of pregnancy, swelling, aching muscles and gastrointestinal upsets. Feverfew – pregnant women should avoid using this herb, as it can trigger uterine contractions which could lead to premature labour or miscarriage. Asteraceae plants – which include feverfew, echinacea and chamomile. Side effects include hay fever. Pharmacogenetics: the use of genetic information to determine which type of drugs will work best for a patient MedEffect Canada definitions.pdf