|Metabolism||Hepatic (mediated by CYP2D6; most metabolism occurs via aromatic hydroxylation, N-oxidation and N-demethylation)|
|Biological half-life||21–61 hours|
|Chemical and physical data|
|3D model (JSmol)|
|(what is this?)|
Mianserin is a tetracyclic antidepressant (TeCA) therapeutic family. It is classified as a noradrenergic and specific serotonergic antidepressant (NaSSA) and was first marketed in 1979. It is chemically related to mirtazapine.
When used for the treatment of depression, its efficacy appears comparable to that of amitriptyline, citalopram, clomipramine, dothiepin, doxepin, fluoxetine, flupenthixol, fluvoxamine, imipramine, moclobemide, nortriptyline, paroxetine, and trazodone. Mianserin received TGA approval in May 1996.
Similarly to its analogue, mirtazapine, mianserin has been tried as an augmentation strategy in treatment-resistant depression with some success. Mianserin has been tried, similarly to mirtazapine, as an adjunct in schizophrenia and has been found to reduce negative and cognitive symptoms.
Common (1%<incidence≤10%) adverse effects include drowsiness during maintenance therapy, tremor, headache, dizziness, vertigo, and weakness.
Uncommon (0.1%<incidence≤1%) adverse effects include weight gain.
CYP2D6 inhibitors such as the selective serotonin reuptake inhibitors (SSRIs), quinidine, ritonavir, etc. would likely raise plasma levels of mianserin and hence could lead to mianserin toxicity. Conversely, CYP2D6 inducers would likely lead to reduced mianserin plasma concentrations and hence potentially diminish the therapeutic effects of mianserin.
Abrupt or rapid discontinuation of mianserin may provoke a withdrawal, the effects of which may include depression, anxiety, panic attacks, decreased appetite or anorexia, insomnia, diarrhea, nausea and vomiting, and flu-like symptoms, such as allergies or pruritus, among others.
Overdose of mianserin is known to produce sedation, coma, hypotension or hypertension, tachycardia, and QT interval prolongation.
Mianserin is an antagonist/inverse agonist of the H1, 5-HT1D, 5-HT2A, 5-HT2B, 5-HT2C, 5-HT3, 5-HT6, 5-HT7, α1-adrenergic, and α2-adrenergic receptors, and also inhibits the reuptake of norepinephrine. As a high affinity H1 receptor inverse agonist, mianserin has strong antihistamine effects (sedation, weight gain, etc.). Contrarily, it has negligible affinity for the mACh receptors, and thus lacks anticholinergic properties. It was recently found to be a weak (Ki = 1.7 μM, EC50 = 0.53 μM) κ-opioid receptor partial agonist.
In addition, mianserin also appears to be a potent antagonist of the neuronal octopamine receptor. What implications this may have on mood are currently unknown, however octopamine has been implicated in the regulation of sleep, appetite and insulin production and therefore may theoretically contribute to the overall side effect profile of mianserin.
Blockade of the H1 and α1-adrenergic receptors has sedative effects, and also antagonism of the 5-HT2A and α1-adrenergic receptors inhibits activation of intracellular phospholipase C (PLC), 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, serotonin, and acetylcholine in various areas of the brain and body.
(S)-(+)-Mianserin is approximately 200–300 times more active than its enantiomer (R)-(−)-mianserin.
|Molecular target||Binding affinity (Ki [nM])|
|α1 adrenoceptor||74 (Cloned rat receptor)|
It was developed but not discovered by Organon; the first patents in issued in The Netherlands in 1967 and it was launched in France in 1979 under the brand name Athymil and soon thereafter in the UK as Norval. Investigators conducting clinical trials in the US submitted fraudulent data, and it was never approved in the US.:21:318
Society and culture
As of June 2017 it was marketed in several countries under the following names: Athmyl, Bonserin, Depnon, Deprexolet, Lantanon, Lerivon, Mealin, Miabene, Miagen, Miansec, Miansegen, Mianserin, Mianserin, Mianserina, Mianserine, Miansérine, Miansérine, Mianserinhydrochlorid, Mianserini, Mianserinum , Prevalina, Tetramide, Tolimed, Tolmin, Tolvon, and Tolvon.
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