Mianserin

Source: Wikipedia, the free encyclopedia.
Not to be confused with ritanserin.
Mianserin
Clinical data
Trade namesTolvon, others
Other namesMianserin hydrochloride; Org GB 94[1][2]
Pregnancy
category
  • AU: B2
Routes of
administration		By mouth
ATC code
Legal status
Legal status
  • AU: S4 (Prescription only)
  • BR: Class C1 (Other controlled substances)[3]
  • UK: POM (Prescription only)
oxidation, N-demethylation)[4]
Elimination half-life21–61 hours[5]
ExcretionUrine: 4–7%[4]
Feces: 14–28%[4]
Identifiers
  • (±)-2-methyl-1,2,3,4,10,14b-hexahydrodibenzo[c,f]pyrazino[1,2-a]azepine
JSmol)
  • c42c(N3C(c1ccccc1C2)CN(C)CC3)cccc4
  • InChI=1S/C18H20N2/c1-19-10-11-20-17-9-5-3-7-15(17)12-14-6-2-4-8-16(14)18(20)13-19/h2-9,18H,10-13H2,1H3 checkY
  • Key:UEQUQVLFIPOEMF-UHFFFAOYSA-N checkY
 ☒NcheckY (what is this?)  (verify)

Mianserin, sold under the brand name Tolvon among others, is an atypical antidepressant that is used primarily in the treatment of depression in Europe and elsewhere in the world.[6] It is a tetracyclic antidepressant (TeCA). Mianserin is closely related to mirtazapine, both chemically and in terms of its actions and effects, although there are significant differences between the two drugs.[7]

Medical uses

Mianserin at higher doses (30–90mg/day) is used for the treatment of major depressive disorder.[6]

It can also be used at lower doses (around 10mg/day) to treat insomnia.[8][9]

Contraindications

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 severe liver disease should not take mianserin, and 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. 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]

Side effects

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]

Withdrawal

Abrupt or rapid discontinuation of mianserin may provoke a

pruritus
, among others.

Overdose

Overdose of mianserin is known to produce sedation, coma, hypotension or hypertension, tachycardia, and QT interval prolongation.[11]

Interactions

Mianserin may enhance the sedative effects of drugs such as alcohol, anxiolytics, hypnotics, or antipsychotics when co-administered. It may decrease the efficacy of

antiepileptic
medications.

antimuscarinics have stronger effects. Mianserin should not be taken with apraclonidine, brimonidine, sibutramine, or the combination drug of artemether with lumefantrine.[6]

Pharmacology

Pharmacodynamics

See also: Pharmacology of antidepressants and Tetracyclic antidepressant § Pharmacology
Mianserin[12]
Site Ki (nM) Species Ref
SERTTooltip Serotonin transporter 4,000 Human [13]
NETTooltip Norepinephrine transporter 71 Human [13]
DATTooltip Dopamine transporter 9,400 Human [13]
5-HT1A 400–2,600 Human [14][15]
5-HT1B ≥2,800 Rat [16]
5-HT1D 220–400 Human [17][18]
5-HT1E ND ND ND
5-HT1F 13 Human [14]
5-HT2A 1.6–55 Human [19][20]
5-HT2B 1.6–20 Human [21][22]
5-HT2C 0.63–6.5 Human [19][23]
5-HT3 5.8–300 Rodent [24][15]
5-HT4 ND ND ND
5-HT5A ND ND ND
5-HT6 55–81 Human [25][26]
5-HT7 48–56 Human [27][28][29]
α1 34 Human [30]
α2 73 Human [30]
  α2A 4.8 Human [27]
  α2B 27 Human [31]
  α2C 3.8 Human [27]
D1
 426–1,420 Human [15][27]
D2
 2,100–2,700 Human [30][32]
D3
 2,840 Human [30]
D4
 ND ND ND
D5
 ND ND ND
H1 0.30–1.7 Human [33][30][27]
H2 437 Human [34]
H3 95,500 Human [34]
H4 >100,000 Human [34][35]
mAChTooltip Muscarinic acetylcholine receptor 820 Human [30]
MOR
Tooltip μ-Opioid receptor		 21,000 Human [36]
DOR
Tooltip δ-Opioid receptor		 30,200 Human [36]
KOR
Tooltip κ-Opioid receptor		 530 (
EC50
Tooltip Half-maximal effective concentration)		 Human [36]
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 of

affinity, mianserin has strong antihistamine effects (e.g., sedation). Conversely, it has low affinity for the muscarinic acetylcholine receptors, and hence lacks anticholinergic properties.[30] Mianserin has been found to be a low affinity but potentially significant partial agonist of the κ-opioid receptor (Ki = 1.7 μM; EC50 = 0.53 μM),[36] similarly to some tricyclic antidepressants (TCAs).[39]

Blockade of the H1 and possibly α1-adrenergic receptors has

inhibitory autoreceptors and heteroreceptors, mianserin disinhibits the release of norepinephrine, dopamine, serotonin, 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 (NaSSA).[41] However, the actual evidence in support of this label has been regarded as poor.[42]

Pharmacokinetics

The

elimination half-life is 21 to 61 hours.[4] The drug is excreted 4 to 7% in the urine and 14 to 28% in feces.[4]

Chemistry

(S)-Mianserin.

Mianserin is a tetracyclic piperazinoazepine. Mirtazapine was developed by the same team of organic chemists and differs via addition of a nitrogen atom in one of the rings.[43][44] (S)-(+)-Mianserin is approximately 200–300 times more active than its enantiomer (R)-(−)-mianserin; hence, the activity of mianserin lies in the (S)-(+) isomer.[citation needed]

History

It was

Organon 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.[45]: 21 [46]
: 318 

Mianserin was one of the first antidepressants to reach the UK market that was less dangerous than the tricyclic antidepressants in overdose; as of 2012 it was not prescribed much in the UK.[47]

Society and culture

Mianserin.

Generic names

Mianserin is the

Latin is mianserinum.[48][1][49][2]

Brand names

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][48]

Availability

Mianserin is not approved for use in the United States, but is available in the United Kingdom and other European countries.[50][51] A mianserin generic drug received TGATooltip Therapeutic Goods Administration approval in May 1996 and is available in Australia.[52]

Research

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.[53][54]

References

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  2. ^ a b c "International brands for mianserin". Drugs.com. Retrieved 20 August 2017.
  3. ^ Anvisa (2023-03-31). "RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial" [Collegiate Board Resolution No. 784 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control] (in Brazilian Portuguese). Diário Oficial da União (published 2023-04-04). Archived from the original on 2023-08-03. Retrieved 2023-08-16.
  4. ^ a b c d e f g h i j Truven Health Analytics, Inc. Drugdex System (Internet) [cited 2013 Sep 29]. Greenwood Village, CO: Thomsen Healthcare; 2013.
  5. ^ a b c d e "Tolvon Product Information" (PDF). Medicines. AU: Merck Sharp & Dohme. Archived from the original (PDF) on 2016-04-02. Retrieved 2013-10-05 – via GuildLink.
  6. ^ a b c d e f g "Mianserin 30 mg film-coated tablets". UK Electronic Medicines Compendium. January 2014. Retrieved 20 August 2017.
  7. ^ "A Comparison of the Physicochemical and Biological Properties of Mirtazapine and Mianserin". Journal of pharmacy and pharmacology. Oxford University Press. April 2011. Retrieved 29 January 2022.
  8. ^ "Que faire devant une insomnie" [What to do when facing insomnia]. Sommeil (in French). Lyon, FR: University of Lyon.
  9. ^ "Traitement des troubles du sommeil" [Treatment of the troubles of sleep]. Research gate (in French). Archived from the original on 2019-03-30.
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  11. ^ Taylor D, Paton C, Kapur S, Taylor D (2012). The Maudsley Prescribing Guidelines in Psychiatry (11th ed.). Chichester, West Sussex: John Wiley & Sons.
  12. ^ Roth BL, Driscol J. "PDSP Ki Database". Psychoactive Drug Screening Program (PDSP). University of North Carolina at Chapel Hill and the United States National Institute of Mental Health. Retrieved 14 August 2017.
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  54. PMID 25240772
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Further reading