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| Trade names | Tolvon, others |
| Other names | Mianserin hydrochloride; Org GB 94[1][2] |
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| Routes of administration | By mouth |
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| Pharmacokinetic data | |
| Bioavailability | 20–30%[4] |
| Protein binding | 95%[4] |
| Metabolism | Liver (CYP2D6; viaaromatichydroxylation,N-oxidation,N-demethylation)[4] |
| Eliminationhalf-life | 21–61 hours[5] |
| Excretion | Urine: 4–7%[4] Feces: 14–28%[4] |
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| ECHA InfoCard | 100.041.884 |
| Chemical and physical data | |
| Formula | C18H20N2 |
| Molar mass | 264.372 g·mol−1 |
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Mianserin, sold under the brand nameTolvon among others, is anatypical antidepressant that is used primarily in the treatment ofdepression inEurope and elsewhere in the world.[6] It is atetracyclic antidepressant (TeCA). Mianserin is closely related tomirtazapine, bothchemically and in terms of its actions and effects, although there are significant differences between the two drugs (for example, its highernoradrenergic activity and lower5-HT3 receptor antagonism).[7]
Mianserin at higher doses (30–90 mg/day) is used for the treatment ofmajor depressive disorder.[6]
It can also be used at lower doses (around 10 mg/day) to treat insomnia.[8][9]
It should not be given, except if based on clinical need and under strict medical supervision, to people younger than 18 years old, as it can increase the risk of suicide attempts and suicidal thinking, and it can increase aggressiveness.[6]
While there is no evidence that it can harm a fetus from animal models, there are no data showing it safe for pregnant women to take.[6]
People with severeliver disease should not take mianserin, and it should be used with caution for people withepilepsy or who are at risk for seizures, as it can lower the threshold for seizures. If based on clinical decision, normal precautions should be exercised and the dosages of mianserin and any concurrent therapy kept under review and adjusted as needed.[6]
Very common (incidence > 10%) adverse effects include constipation, dry mouth, and drowsiness at the beginning of treatment.[5][6]
Common (1% < incidence ≤ 10%) adverse effects include drowsiness during maintenance therapy, tremor, headache, dizziness, vertigo, and weakness.[5]
Uncommon (0.1% < incidence ≤ 1%) adverse effects include weight gain.[5]
Abrupt or rapid discontinuation of mianserin may provoke awithdrawal, theeffects of which may includedepression,anxiety,panic attacks,[10] decreasedappetite oranorexia,insomnia,diarrhea,nausea andvomiting, andflu-like symptoms, such asallergies orpruritus, among others.
Overdose of mianserin is known to produce sedation, coma, hypotension or hypertension, tachycardia, and QT interval prolongation.[11]
Mianserin may enhance the sedative effects of drugs such asalcohol, anxiolytics, hypnotics, or antipsychotics when co-administered. It may decrease the efficacy ofantiepileptic medications.
Carbamazepine andphenobarbital 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 withdiazoxide,hydralazine, ornitroprusside. Mianserin can makeantihistamines andantimuscarinics have stronger effects. Mianserin should not be taken withapraclonidine,brimonidine,sibutramine, or the combination drug ofartemether withlumefantrine.[6]
| Site | Ki (nM) | Species | Ref |
|---|---|---|---|
| SERTTooltip Serotonin transporter | 4000 | Human | [13] |
| NETTooltip Norepinephrine transporter | 71 | Human | [13] |
| DATTooltip Dopamine transporter | 9400 | Human | [13] |
| 5-HT1A | 400–2600 | Human | [14][15] |
| 5-HT1B | 2800–4700 | Rat | [16][17] |
| 5-HT1D | 220–400 | Human | [18][19] |
| 5-HT1E | ND | ND | ND |
| 5-HT1F | 13 | Human | [14] |
| 5-HT2A | 1.6–55 | Human | [20][21] |
| 5-HT2B | 1.6–20 | Human | [22][23] |
| 5-HT2C | 0.63–6.5 | Human | [20][24] |
| 5-HT3 | 5.8–300 | Rodent | [25][15] |
| 5-HT4 | ND | ND | ND |
| 5-HT5A | ND | ND | ND |
| 5-HT6 | 55–81 | Human | [26][27] |
| 5-HT7 | 48–56 | Human | [28][29][30] |
| α1 | 34 | Human | [31] |
| α2 | 73 | Human | [31] |
| α2A | 4.8 | Human | [28] |
| α2B | 27 | Human | [32] |
| α2C | 3.8 | Human | [28] |
| D1 | 426–1420 | Human | [15][28] |
| D2 | 2100–2700 | Human | [31][33] |
| D3 | 2840 | Human | [31] |
| D4 | ND | ND | ND |
| D5 | ND | ND | ND |
| H1 | 0.30–1.7 | Human | [34][31][28] |
| H2 | 437 | Human | [35] |
| H3 | 95500 | Human | [35] |
| H4 | 100000+ | Human | [35][36] |
| mAChTooltip Muscarinic acetylcholine receptor | 820 | Human | [31] |
| MORTooltip μ-Opioid receptor | 21000 | Human | [37] |
| DORTooltip δ-Opioid receptor | 30200 | Human | [37] |
| KORTooltip κ-Opioid receptor | 530 (EC50Tooltip Half-maximal effective concentration) | Human | [37] |
| Values are Ki (nM), unless otherwise noted. The smaller the value, the more strongly the drug binds to the site. | |||
Mianserin appears to exert its effects via antagonism ofhistamine andserotonin receptors, and inhibition ofnorepinephrine reuptake. More specifically, it is anantagonist/inverse agonist at most, if not all sites of thehistamineH1 receptor,serotonin5-HT1D,5-HT1F,5-HT2A,5-HT2B,5-HT2C,5-HT3,5-HT6, and5-HT7 receptors, and adrenergicα1- andα2-adrenergic receptors, and additionally anorepinephrinereuptake inhibitor.[38][39][17] As an H1 receptor inverse agonist with highaffinity, mianserin has strongantihistamine effects (e.g.,sedation). Conversely, it has low affinity for themuscarinic acetylcholine receptors, and hence lacksanticholinergic properties.[31] Mianserin has been found to be a low affinity but potentially significantpartial agonist of theκ-opioid receptor (Ki = 1.7 μM;EC50 = 0.53 μM),[37] similarly to sometricyclic antidepressants (TCAs).[40]
Blockade of the H1 and possibly α1-adrenergic receptors hassedative effects,[5] and also antagonism of the 5-HT2A and α1-adrenergic receptors inhibits activation ofintracellularphospholipase C (PLC), which seems to be a common target for several differentclasses ofantidepressants.[41] By antagonizing thesomatodendritic andpresynaptic α2-adrenergic receptors, which function predominantly asinhibitoryautoreceptors andheteroreceptors, mianserin disinhibits the release ofnorepinephrine,dopamine,serotonin, andacetylcholine in various areas of thebrain andbody.
Along with mirtazapine, although to a lesser extent in comparison, mianserin has sometimes been described as anoradrenergic and specific serotonergic antidepressant (NaSSA).[42] However, the actual evidence in support of this label has been regarded as poor.[43]
Thebioavailability of mianserin is 20 to 30%.[4] Itsplasma protein binding is 95%.[4] Mianserin ismetabolized in theliver by theCYP2D6enzyme viaN-oxidation andN-demethylation.[4] Itselimination half-life is 21 to 61 hours.[4] The drug isexcreted 4 to 7% in theurine and 14 to 28% infeces.[4]
Mianserin is a tetracyclicpiperazinoazepine.Mirtazapine was developed by the same team of organic chemists and differs via addition of a nitrogen atom in one of the rings.[44][45] (S)-(+)-Mianserin is approximately 200–300 times more active than itsenantiomer (R)-(−)-mianserin; hence, the activity of mianserin lies in the (S)-(+)isomer.[citation needed]
It wasdeveloped but not discovered byOrganon International; the first patents were 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.[46]: 21 [47]: 318
Mianserin was one of the first antidepressants to reach the UK market that was less dangerous than thetricyclic antidepressants in overdose; as of 2012 it was not prescribed much in the UK.[48]
Mianserin is theEnglish andGermangeneric name of the drug and itsINNTooltip International Nonproprietary Name andBANTooltip British Approved Name, whilemianserin hydrochloride is itsUSANTooltip United States Adopted Name,BANMTooltip British Approved Name, andJANTooltip Japanese Accepted Name. Its generic name inFrench and itsDCFTooltip Dénomination Commune Française aremiansérine, inSpanish andItalian and itsDCITTooltip Denominazione Comune Italiana aremianserina, and inLatin ismianserinum.[49][1][50][2]
Mianserin is marketed in many countries mainly under the brand name Tolvon. It is also available throughout the world under a variety of other brand names including Athymil, Bonserin, Bolvidon, Deprevon, Lantanon, Lerivon, Lumin, Miansan, Serelan, Tetramide, and Tolvin among others.[1][2][49]
Mianserin is not approved for use in theUnited States, but is available in theUnited Kingdom and otherEuropean countries.[51][52] A mianserin generic drug receivedTGATooltip Therapeutic Goods Administration approval in May 1996 and is available inAustralia.[53]
The use of mianserin to help people with schizophrenia who are being treated with antipsychotics has been studied in clinical trials; the outcome is unclear.[54][55]
Table II. Affinities of Selected Phenalkylamines for 5-HT1 and 5-HT2 Binding Sites