An autoreceptor is a type of receptor located in the membranes of presynaptic nerve cells. It serves as part of a negative feedback loop in signal transduction, it is only sensitive to the neurotransmitters or hormones released by the neuron on which the autoreceptor sits. A heteroreceptor is sensitive to neurotransmitters and hormones that are not released by the cell on which it sits. A given receptor can act as either an autoreceptor or a heteroreceptor, depending upon the type of transmitter released by the cell on which it is embedded. Autoreceptors may be located in any part of the cell membrane: in the dendrites, the cell body, the axon, or the axon terminals. Canonically, a presynaptic neuron releases a neurotransmitter across a synaptic cleft to be detected by the receptors on a postsynaptic neuron. Autoreceptors on the presynaptic neuron will detect this neurotransmitter and function to control internal cell processes inhibiting further release or synthesis of the neurotransmitter. Thus, release of neurotransmitter is regulated by negative feedback.
Autoreceptors are G protein-coupled receptors and act via a second messenger. As an example, norepinephrine released from sympathetic neurons may interact with the alpha-2A and alpha-2C adrenoreceptors to inhibit further release of norepinephrine. Acetylcholine released from parasympathetic neurons may interact with M2 and M4 receptors to inhibit further release of acetylcholine. An atypical example is given by the β-adrenergic autoreceptor in the sympathetic peripheral nervous system, which acts to increase transmitter release; the D2sh autoreceptor interacts with the trace amine-assorted receptor 1, a discovered GPCR, to regulate monoaminergic systems in the brain. Active TAAR1 opposes the autoreceptor's activity by inactivating the dopamine transporter. In their review of TAAR1 in monoaminergic systems and Miller proposed this schematic: synaptic dopamine binds to the dopamine autoreceptor, which activates the DAT. Dopamine enters the presynaptic binds to TAAR1, which increases adenylyl cyclase activity.
This allows for the translation of trace amines in the cytoplasm and activation of cyclic nucleotide-gated ion channels, which further activate TAAR1 and dump dopamine into the synapse. Through a series of phosphorylation events related to PKA and PKC, active TAAR1 inactivates DAT, preventing uptake of dopamine from the synapse; the presence of two Postsynaptic receptors with opposite abilities to regulate monoamine transporter function allows for regulation of the monoaminergic system. Autoreceptor activity may decrease paired-pulse facilitation. A feedback cell is activated by the depolarized post-synaptic neuron; the feedback cell releases a neurotransmitter to which the autoreceptor of the presynaptic neuron is receptive. The autoreceptor causes the inhibition of calcium channels and the opening of potassium channels in the presynaptic membrane; these changes in ion concentration diminish the amount of the original neurotransmitter released by the presynaptic terminal into the synaptic cleft.
This causes a final depression on the activity of the postsynaptic neuron. Thus the feedback cycle is complete
Simplified molecular-input line-entry system
The simplified molecular-input line-entry system is a specification in the form of a line notation for describing the structure of chemical species using short ASCII strings. SMILES strings can be imported by most molecule editors for conversion back into two-dimensional drawings or three-dimensional models of the molecules; the original SMILES specification was initiated in the 1980s. It has since been extended. In 2007, an open standard called. Other linear notations include the Wiswesser line notation, ROSDAL, SYBYL Line Notation; the original SMILES specification was initiated by David Weininger at the USEPA Mid-Continent Ecology Division Laboratory in Duluth in the 1980s. Acknowledged for their parts in the early development were "Gilman Veith and Rose Russo and Albert Leo and Corwin Hansch for supporting the work, Arthur Weininger and Jeremy Scofield for assistance in programming the system." The Environmental Protection Agency funded the initial project to develop SMILES. It has since been modified and extended by others, most notably by Daylight Chemical Information Systems.
In 2007, an open standard called "OpenSMILES" was developed by the Blue Obelisk open-source chemistry community. Other'linear' notations include the Wiswesser Line Notation, ROSDAL and SLN. In July 2006, the IUPAC introduced the InChI as a standard for formula representation. SMILES is considered to have the advantage of being more human-readable than InChI; the term SMILES refers to a line notation for encoding molecular structures and specific instances should be called SMILES strings. However, the term SMILES is commonly used to refer to both a single SMILES string and a number of SMILES strings; the terms "canonical" and "isomeric" can lead to some confusion when applied to SMILES. The terms are not mutually exclusive. A number of valid SMILES strings can be written for a molecule. For example, CCO, OCC and CC all specify the structure of ethanol. Algorithms have been developed to generate the same SMILES string for a given molecule; this SMILES is unique for each structure, although dependent on the canonicalization algorithm used to generate it, is termed the canonical SMILES.
These algorithms first convert the SMILES to an internal representation of the molecular structure. Various algorithms for generating canonical SMILES have been developed and include those by Daylight Chemical Information Systems, OpenEye Scientific Software, MEDIT, Chemical Computing Group, MolSoft LLC, the Chemistry Development Kit. A common application of canonical SMILES is indexing and ensuring uniqueness of molecules in a database; the original paper that described the CANGEN algorithm claimed to generate unique SMILES strings for graphs representing molecules, but the algorithm fails for a number of simple cases and cannot be considered a correct method for representing a graph canonically. There is no systematic comparison across commercial software to test if such flaws exist in those packages. SMILES notation allows the specification of configuration at tetrahedral centers, double bond geometry; these are structural features that cannot be specified by connectivity alone and SMILES which encode this information are termed isomeric SMILES.
A notable feature of these rules is. The term isomeric SMILES is applied to SMILES in which isotopes are specified. In terms of a graph-based computational procedure, SMILES is a string obtained by printing the symbol nodes encountered in a depth-first tree traversal of a chemical graph; the chemical graph is first trimmed to remove hydrogen atoms and cycles are broken to turn it into a spanning tree. Where cycles have been broken, numeric suffix labels are included to indicate the connected nodes. Parentheses are used to indicate points of branching on the tree; the resultant SMILES form depends on the choices: of the bonds chosen to break cycles, of the starting atom used for the depth-first traversal, of the order in which branches are listed when encountered. Atoms are represented by the standard abbreviation of the chemical elements, in square brackets, such as for gold. Brackets may be omitted in the common case of atoms which: are in the "organic subset" of B, C, N, O, P, S, F, Cl, Br, or I, have no formal charge, have the number of hydrogens attached implied by the SMILES valence model, are the normal isotopes, are not chiral centers.
All other elements must be enclosed in brackets, have charges and hydrogens shown explicitly. For instance, the SMILES for water may be written as either O or. Hydrogen may be written as a separate atom; when brackets are used, the symbol H is added if the atom in brackets is bonded to one or more hydrogen, followed by the number of hydrogen atoms if greater than 1 by the sign + for a positive charge or by - for a negative charge. For example, for ammonium. If there is more than one charge, it is written as digit.
A receptor antagonist is a type of receptor ligand or drug that blocks or dampens a biological response by binding to and blocking a receptor rather than activating it like an agonist. They are sometimes called blockers. In pharmacology, antagonists have affinity but no efficacy for their cognate receptors, binding will disrupt the interaction and inhibit the function of an agonist or inverse agonist at receptors. Antagonists mediate their effects by binding to the active site or to the allosteric site on a receptor, or they may interact at unique binding sites not involved in the biological regulation of the receptor's activity. Antagonist activity may be reversible or irreversible depending on the longevity of the antagonist–receptor complex, which, in turn, depends on the nature of antagonist–receptor binding; the majority of drug antagonists achieve their potency by competing with endogenous ligands or substrates at structurally defined binding sites on receptors. The English word antagonist in pharmaceutical terms comes from the Greek ἀνταγωνιστής – antagonistēs, "opponent, villain, rival", derived from anti- and agonizesthai.
Biochemical receptors are large protein molecules that can be activated by the binding of a ligand such as a hormone or a drug. Receptors can be membrane-bound, as cell surface receptors, or inside the cell as intracellular receptors, such as nuclear receptors including those of the mitochondrion. Binding occurs as a result of non-covalent interactions between the receptor and its ligand, at locations called the binding site on the receptor. A receptor may contain one or more binding sites for different ligands. Binding to the active site on the receptor regulates receptor activation directly; the activity of receptors can be regulated by the binding of a ligand to other sites on the receptor, as in allosteric binding sites. Antagonists mediate their effects through receptor interactions by preventing agonist-induced responses; this may be accomplished by binding to the allosteric site. In addition, antagonists may interact at unique binding sites not involved in the biological regulation of the receptor's activity to exert their effects.
The term antagonist was coined to describe different profiles of drug effects. The biochemical definition of a receptor antagonist was introduced by Ariens and Stephenson in the 1950s; the current accepted definition of receptor antagonist is based on the receptor occupancy model. It narrows the definition of antagonism to consider only those compounds with opposing activities at a single receptor. Agonists were thought to turn "on" a single cellular response by binding to the receptor, thus initiating a biochemical mechanism for change within a cell. Antagonists were thought to turn "off" that response by'blocking' the receptor from the agonist; this definition remains in use for physiological antagonists, substances that have opposing physiological actions, but act at different receptors. For example, histamine lowers arterial pressure through vasodilation at the histamine H1 receptor, while adrenaline raises arterial pressure through vasoconstriction mediated by alpha-adrenergic receptor activation.
Our understanding of the mechanism of drug-induced receptor activation and receptor theory and the biochemical definition of a receptor antagonist continues to evolve. The two-state model of receptor activation has given way to multistate models with intermediate conformational states; the discovery of functional selectivity and that ligand-specific receptor conformations occur and can affect interaction of receptors with different second messenger systems may mean that drugs can be designed to activate some of the downstream functions of a receptor but not others. This means efficacy may depend on where that receptor is expressed, altering the view that efficacy at a receptor is receptor-independent property of a drug. By definition, antagonists display no efficacy to activate the receptors they bind. Antagonists do not maintain the ability to activate a receptor. Once bound, antagonists inhibit the function of agonists, inverse agonists, partial agonists. In functional antagonist assays, a dose-response curve measures the effect of the ability of a range of concentrations of antagonists to reverse the activity of an agonist.
The potency of an antagonist is defined by its half maximal inhibitory concentration. This can be calculated for a given antagonist by determining the concentration of antagonist needed to elicit half inhibition of the maximum biological response of an agonist. Elucidating an IC50 value is useful for comparing the potency of drugs with similar efficacies, however the dose-response curves produced by both drug antagonists must be similar; the lower the IC50 the greater the potency of the antagonist, the lower the concentration of drug, required to inhibit the maximum biological response. Lower concentrations of drugs may be associated with fewer side-effects; the affinity of an antagonist for its binding site, i.e. its ability to bind to a receptor, will determine the duration of inhibition of agonist activity. The affinity of an antagonist can be determined experimentally using Schild regression or for competitive antagonists in radioligand binding studies using the Cheng-Prusoff equation. Schild regression can be used to determine the nature of antagonism as beginning either competitive or non-competitive and Ki determination is independent of the affinity, efficacy or concentration of the agonist used.
However, it is important. The effects of receptor desensitization on reaching equilibrium must als
Levomilnacipran is an antidepressant, approved in the United States in 2013 for the treatment of major depressive disorder in adults. It is the levorotatory enantiomer of milnacipran, has similar effects and pharmacology, acting as a serotonin–norepinephrine reuptake inhibitor; the FDA approved levomilnacipran for the treatment of major depressive disorder based on the results of one 10-week phase II and four 8-week phase III clinical trials. Four of the five trials demonstrated a statistically significant superiority to placebo as measured by the Montgomery–Åsberg Depression Rating Scale. Superiority to placebo was demonstrated by improvement in the Sheehan Disability Scale. Side effects seen more with levomilnacipran than with placebo in clinical trials included nausea, sweating, insomnia, increased heart rate and blood pressure, urinary hesitancy, erectile dysfunction and delayed ejaculation in males, vomiting and palpitations. Relative to other SNRIs, levomilnacipran, as well as milnacipran, differ in that they are much more balanced reuptake inhibitors of serotonin and norepinephrine.
To demonstrate, the serotonin:norepinephrine ratios of SNRIs are as follows: venlafaxine = 30:1, duloxetine = 10:1, desvenlafaxine = 14:1, milnacipran = 1.6:1, levomilnacipran = 1:2. The clinical implications of more balanced elevations of serotonin and norepinephrine are unclear, but may include improved effectiveness, though increased side effects. Levomilnacipran is selective for the serotonin and norepinephrine transporters, lacking significant affinity for over 23 off-target sites. However, it does show some affinity for the dizocilpine site of the NMDA receptor, has been found to inhibit NR2A and NR2B subunit-containing NMDA receptors with respective IC50 values of 5.62 and 4.57 µM. As such, levomilnacipran is an NMDA receptor antagonist at high concentrations. Levomilnacipran has been found to act as an inhibitor of beta-site amyloid precursor protein cleaving enzyme-1, responsible for β-amyloid plaque formation, hence may be a useful drug in the treatment of Alzheimer's disease. Levomilnacipran has a high oral bioavailability of 92% and a low plasma protein binding of 22%.
It is metabolized in the liver by the cytochrome P450 enzyme CYP3A4, thereby making the medication susceptible to grapefruit-drug interactions. The drug has an elimination half-life of 12 hours, allowing for once-daily administration. Levomilnacipran is excreted in urine. Levomilnacipran was developed by Forest Laboratories and Pierre Fabre Group, was approved by the Food and Drug Administration in July 2013. Media related to Levomilnacipran at Wikimedia Commons Fetzima Official Site
Venlafaxine, sold under the brand name Effexor among others, is an antidepressant medication of the serotonin-norepinephrine reuptake inhibitor class. It is used to treat major depressive disorder, generalized anxiety disorder, panic disorder, social phobia, it is taken by mouth. Common side effects include loss of appetite, dry mouth, dizziness and sexual problems. Severe side effects include an increased risk of suicide and serotonin syndrome. Antidepressant withdrawal syndrome may occur. There are concerns that use during the part of pregnancy can harm the baby. How it works is not clear but it is believed to involve alterations in neurotransmitters in the brain. Venlafaxine was approved for medical use in the United States in 1993, it is available as a generic medication. In the United States the wholesale cost per dose is less than US$0.20 as of 2018. In 2016 it was the 51st most prescribed medication in the United States with more than 15 million prescriptions. Venlafaxine is used for the treatment of depression, general anxiety disorder, social phobia, panic disorder, vasomotor symptoms.
Some doctors may prescribe venlafaxine off label for the treatment of diabetic neuropathy and migraine prophylaxis. Studies have shown venlafaxine's effectiveness for these conditions, although agents that are marketed for this purpose are preferred, it has been found to reduce the severity of'hot flashes' in menopausal women and men on hormonal therapy for the treatment of prostate cancer. Due to its action on both the serotoninergic and adrenergic systems, venlafaxine is used as a treatment to reduce episodes of cataplexy, a form of muscle weakness, in patients with the sleep disorder narcolepsy; some open-label and three double-blind studies have suggested the efficacy of venlafaxine in the treatment of attention deficit-hyperactivity disorder. Clinical trials have found possible efficacy in those with post-traumatic stress disorder. A comparative meta-analysis of 21 major antidepressants found that venlafaxine, amitriptyline, mirtazapine and vortioxetine were more effective than other antidepressants although the quality of many comparisons was assessed as low or low.
Venlafaxine was similar in efficacy to the atypical antidepressant bupropion. In a double-blind study, patients who did not respond to an SSRI were switched to venlafaxine or citalopram. Similar improvement was observed in both groups. Studies of venlafaxine in children have not established its efficacy. Venlafaxine is not recommended in patients hypersensitive to it, nor should it be taken by anyone, allergic to the inactive ingredients, which include gelatin, ethylcellulose, iron oxide, titanium dioxide and hypromellose, it should not be used in conjunction with a monoamine oxidase inhibitor, as it can cause fatal serotonin syndrome. Venlafaxine can increase eye pressure, so those with glaucoma may require more frequent eye checks; the US Food and Drug Administration body requires all antidepressants, including venlafaxine, to carry a black box warning with a generic warning about a possible suicide risk. A 2014 meta analysis of 21 clinical trials of venlafaxine for the treatment of depression in adults found that compared to placebo, venlafaxine reduced the risk of suicidal thoughts and behavior.
A study conducted in Finland followed more than 15,000 patients for 3.4 years. Venlafaxine increased suicide risk by 60%, as compared to no treatment. At the same time, fluoxetine halved the suicide risk. In another study, the data on more than 200,000 cases were obtained from the UK general practice research database. At baseline, patients prescribed venlafaxine had a greater number of risk factors for suicide than patients treated with other anti-depressants; the patients taking venlafaxine had higher risk of completed suicide than the ones on fluoxetine or citalopram. After adjusting for known risk factors, venlafaxine was associated with an increased risk of suicide relative to fluoxetine and dothiepin, not statistically significant. A statistically significant greater risk for attempted suicide remained after adjustment, but the authors concluded that it could be due to residual confounding. An analysis of clinical trials by the FDA statisticians showed the incidence of suicidal behaviour among the adults on venlafaxine to be not different from fluoxetine or placebo.
Venlafaxine is contraindicated in children and young adults. According to the FDA analysis of clinical trials venlafaxine caused a statistically significant 5-fold increase in suicidal ideation and behaviour in persons younger than 25. In another analysis, venlafaxine was no better than placebo among children, but improved depression in adolescents. However, in both groups and suicidal behaviour increased in comparison to those receiving a placebo. In a study involving antidepressants that had failed to produce results in depressed teenagers, teens whose SSRI treatment had failed who were randomly switched to either another SSRI or to venlafaxine showed an increased rate of suicide on venlafaxine. Among teenagers who were suicidal at the beginning of the study, the rate of suicidal attempts and self-harm was higher, by about 60%, after the switch to venlafaxine than after the switch to an SSRI. People stopping venlafaxine experience discontinuation symptoms such as dysphoria, hea
Regulation of therapeutic goods
The regulation of therapeutic goods, drugs and therapeutic devices, varies by jurisdiction. In some countries, such as the United States, they are regulated at the national level by a single agency. In other jurisdictions they are regulated at the state level, or at both state and national levels by various bodies, as is the case in Australia; the role of therapeutic goods regulation is designed to protect the health and safety of the population. Regulation is aimed at ensuring the safety and efficacy of the therapeutic goods which are covered under the scope of the regulation. In most jurisdictions, therapeutic goods must be registered. There is some degree of restriction of the availability of certain therapeutic goods depending on their risk to consumers. Modern drug regulation has historical roots in the response to the proliferation of universal antidotes which appeared in the wake of Mithridates' death. Mithridates had brought together physicians and shamans to concoct a potion that would make him immune to poisons.
Following his death, the Romans became keen on further developing the Mithridates potion's recipe. Mithridatium re-entered western society through multiple means; the first was through the Leechbook of the Bald, written somewhere between 900 and 950, which contained a formula for various remedies, including for a theriac. Additionally, theriac became a commercial good traded throughout Europe based on the works of Greek and Roman physicians; the resulting proliferation of various recipes needed to be curtailed in order to ensure that people were not passing off fake antidotes, which led to the development of government involvement and regulation. Additionally, the creation of these concoctions took on ritualistic form and were created in public and the process was observed and recorded, it was believed that if the concoction proved unsuccessful, it was due to the apothecaries’ process of making them and they could be held accountable because of the public nature of the creation. In the 9th century, many Muslim countries established an office of the hisba, which in addition to regulating compliance to Islamic principles and values took on the role of regulating other aspects of social and economic life, including the regulation of medicines.
Inspectors were appointed to employ oversight on those who were involved in the process of medicine creation and were given a lot of leigh weigh to ensure compliance and punishments were stringent. The first official'act', the'Apothecary Wares and Stuffs' Act was passed in 1540 by Henry VIII and set the foundation for others. Through this act, he encouraged physicians in his College of Physicians to appoint four people dedicated to inspecting what was being sold in apothecary shops. In conjunction with this first piece of legislation, there was an emergence of standard formulas for the creation of certain ‘drugs’ and ‘antidotes’ through Pharmacopoeias which first appeared in the form of a decree from Frederick II of Sicily in 1240 to use consistent and standard formulas; the first modern pharmacopoeias were the Florence Pharmacopoeia published in 1498, the Spanish Pharmacopoeia published in 1581 and the London Pharmacopoeia published in 1618. In the United States, regulation of drugs was a state right, as opposed to federal right.
But with the increase in fraudulent practices due to private incentives to maximize profits and poor enforcement of state laws, increased the need for stronger federal regulation. President Roosevelt signed the Federal Food and Drug Act in 1906 which established stricter standards. A 1911 Supreme Court decision, United States vs. Johnson, established that misleading statements were not covered under the FFDA; this directly led to Congress passing the Sherley Amendment which established a clearer definition of ‘misbranded’. Another key catalyst for advances in drug regulation were certain catastrophes that served as calls to the government to step in and impose regulations that would prevent repeats of those instances. One such instance occurred in 1937 when more than a hundred people died from using sulfanilamide elixir which had not gone through any safety testing; this directly led to the passing of the Federal, Food and Cosmetic Act in 1938. One other major catastrophe occurred in the late 1950s when Thalidomide, sold in Germany and sold around the world, led to 100,000 babies being born with various deformities.
The UK's Chief Medical Officer had established a group to look into safety of drugs on the market in 1959 prior to the crisis and was moving in the direction of address the problem of unregulated drugs entering the market. The crisis created a greater sense of emergency to establish safety and efficacy standards around the world; the UK started a temporary Committee on Safety of Drugs while they attempted to pass more comprehensive legislation. Though compliance and submission of drugs to the Committee on Safety of Drugs was not mandatory after, the pharmaceutical industry larger complied due to the thalidomide situation; the European Economic Commission passed a directive in 1965 in order to impose greater efficacy standards before marketing a drug. The United States congress passed the Drug Amendments Act of 1962 The Drug Amendments Act required the FDA to ensure that new drugs being introduced to the market had passed certain tests and standards. Both the EU and US acts introduced the requirements to ensure efficacy.
Of note, increased regulations and standards for testing led to greater innovation in pharm
Mianserin, sold under the brand name Tolvon among others, is an atypical antidepressant, used in the treatment of depression in Europe and elsewhere in the world. It is a tetracyclic antidepressant. Mianserin is related to mirtazapine, both chemically and in terms of its actions and effects, although there are significant differences between the two drugs. Mianserin at higher doses is used for the treatment of major depressive disorder, it can be used at lower doses to treat insomnia. It should not be given to be people younger than 18 years old, as it can increase the risk of suicide attempts and suicidal thinking, it can increase aggressiveness. While there is no evidence that it can harm a fetus from animal models, there is no data showing it safe for pregnant women to take. People with severe liver disease should not take mianserin, it should be used with caution for people with epilepsy or who are at risk for seizures, as it can lower the threshold for seizures. Common adverse effects include constipation, dry mouth, drowsiness at the beginning of treatment.
Common adverse effects include drowsiness during maintenance therapy, headache, dizziness and weakness. Uncommon adverse effects include weight gain. Abrupt or rapid discontinuation of mianserin may provoke a withdrawal, the effects of which may include depression, panic attacks, decreased appetite or anorexia, diarrhea and vomiting, flu-like symptoms, such as allergies or pruritus, among others. Overdose of mianserin is known to produce sedation, hypotension or hypertension, QT interval prolongation. Mianserin may make drugs that have effects on the brain, like alcohol, anxiolytics and antipsychotics, have stronger effects, it can make antiepileptic medicines work less well. People should not take monoamine oxidase inhibitors and mianserin at the same time. Carbamazepine and phenobarbital will cause the body to metabolize mianserin faster and may reduce its effects. There is a risk of dangerously low blood pressure if people take mianserin along with diazoxide, hydralazine, or nitroprusside. Mianserin can make antimuscarinics have stronger effects.
Mianserin should not be taken with apraclonidine, sibutramine, or the combination drug of artemether with lumefantrine. Mianserin appears to exert its effects via antagonism of histamine and serotonin receptors, inhibition of norepinephrine reuptake. More it is an antagonist/inverse agonist at most or all sites of the histamine H1 receptor, serotonin 5-HT1D, 5-HT1F, 5-HT2A, 5-HT2B, 5-HT2C, 5-HT3, 5-HT6, 5-HT7 receptors, adrenergic α1- and α2-adrenergic receptors, additionally a norepinephrine reuptake inhibitor; as an H1 receptor inverse agonist with high affinity, mianserin has strong antihistamine effects. Conversely, it has low affinity for the muscarinic acetylcholine receptors, hence lacks anticholinergic properties. Mianserin has been found to be a low affinity but significant partial agonist of the κ-opioid receptor to some tricyclic antidepressants. Blockade of the H1 and α1-adrenergic receptors has sedative effects, antagonism of the 5-HT2A and α1-adrenergic receptors inhibits activation of intracellular phospholipase C, which seems to be a common target for several different classes of antidepressants.
By antagonizing the somatodendritic and presynaptic α2-adrenergic receptors which function predominantly as inhibitory autoreceptors and heteroreceptors, mianserin disinhibits the release of norepinephrine, dopamine and acetylcholine in various areas of the brain and body. Along with mirtazapine, although to a lesser extent in comparison, mianserin has sometimes been described as a noradrenergic and specific serotonergic antidepressant. However, the actual evidence in support of this label has been regarded as poor; the bioavailability of mianserin is 20 to 30%. Its plasma protein binding is 95%. Mianserin is metabolized in the liver by the CYP2D6 enzyme via N-demethylation, its elimination half-life is 21 to 61 hours. The drug is excreted 14 to 28 % in feces. Mianserin is a tetracyclic piperazinoazepine. --Mianserin is 200–300 times more active than its enantiomer --mianserin. It was not discovered by Organon International. Investigators conducting clinical trials in the US submitted fraudulent data, it was never approved in the US.
Mianserin was one of the first antidepressants to reach the UK market, less dangerous than the tricyclic antidepressants in overdose. Mianserin is the English and German generic name of the drug and its INN and BAN, while mianserin hydrochloride is its USAN, BANM, JAN, its generic name in French and its DCF are miansérine, in Spanish and Italian and its DCIT are mianserina, in Latin is mianserinum. Mianserin is marketed in many countries under the brand name Tolvon, it is available throughout the world under a variety of other brand names including Athymil, Deprevon, Lerivon, Serelan and Tolvin among others. Mianserin is not approved for use in the United States, but is available in the United Kin