Mianserin: Difference between revisions

{{Short description|Antidepressant}}

{{cs1 config|name-list-style=vanc}}

{{Distinguish|ritanserin}}

| Verifiedfields = changed

| Watchedfields = changed

| verifiedrevid = 420283195

| IUPAC_name = (±)-2-methyl-1,2,3,4,10,14b-hexahydrodibenzo[''c'',''f'']pyrazino[1,2-''a'']azepine

| image = Mianserin 2D structure.svg

| width = 175px

| image2 = Mianserin ball-and-stick model.png

| width2 = 175px

<!--Clinical data-->| tradename = Tolvon, others

| pregnancy_AU = B2

| pregnancy_US =

| legal_AU = S4

| legal_BR = C1

| legal_BR_comment = <ref>{{Cite web |author=Anvisa |author-link=Brazilian Health Regulatory Agency |date=2023-03-31 |title=RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial |trans-title=Collegiate Board Resolution No. 784 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control|url=https://www.in.gov.br/en/web/dou/-/resolucao-rdc-n-784-de-31-de-marco-de-2023-474904992 |url-status=live |archive-url=https://web.archive.org/web/20230803143925/https://www.in.gov.br/en/web/dou/-/resolucao-rdc-n-784-de-31-de-marco-de-2023-474904992 |archive-date=2023-08-03 |access-date=2023-08-16 |publisher=[[Diário Oficial da União]] |language=pt-BR |publication-date=2023-04-04}}</ref>

| legal_UK = POM

| legal_US =

| routes_of_administration = [[Oral administration|By mouth]]

<!-- Pharmacokinetic data -->| bioavailability = 20–30%<ref name = "DD">Truven Health Analytics, Inc. Drugdex System (Internet) [cited 2013 Sep 29]. Greenwood Village, CO: Thomsen Healthcare; 2013.</ref>

| protein_bound = 95%<ref name = "DD" />

| metabolism = [[Liver]] ([[CYP2D6]]; via [[aromatic compound |aromatic]] [[hydroxylation]], ''N''-[[oxidation]], ''N''-[[demethylation]])<ref name = "DD" />

| elimination_half-life = 21–61 hours<ref name = "TOLVON" />

| excretion = [[Urine]]: 4–7%<ref name = "DD" /><br />[[Feces]]: 14–28%<ref name = "DD" />

<!--Identifiers-->| CAS_number_Ref = {{cascite|correct|??}}

| CAS_number = 24219-97-4

| CAS_supplemental = <br />21535-47-7 ([[hydrochloride]])<br />51152-88-6 ((''S'')-[[isomer]])

| ATC_prefix = N06

| ATC_suffix = AX03

| PubChem = 4184

| IUPHAR_ligand = 135

| DrugBank_Ref = {{drugbankcite|changed|drugbank}}

| DrugBank = DB06148

| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}

| ChemSpiderID = 4040

| UNII_Ref = {{fdacite|correct|FDA}}

| UNII = 250PJI13LM

| KEGG_Ref = {{keggcite|correct|kegg}}

| KEGG = D08216

| ChEBI_Ref = {{ebicite|changed|EBI}}

| ChEBI = 51137

| ChEMBL_Ref = {{ebicite|correct|EBI}}

| ChEMBL = 6437

| synonyms = Mianserin hydrochloride; Org GB 94<ref name= "IndexNominum2000" /><ref name="Drugs.com" />

<!--Chemical data-->| C = 18

| H = 20

| N = 2

| SMILES = c42c(N3C(c1ccccc1C2)CN(C)CC3)cccc4

| StdInChI_Ref = {{stdinchicite|correct|chemspider}}

| StdInChI = 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

| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}

| StdInChIKey = UEQUQVLFIPOEMF-UHFFFAOYSA-N

'''Mianserin''', sold under the brand name '''Tolvon''' among others, is an [[atypical antidepressant]] that is used primarily in the treatment of [[depression (mood)|depression]] in [[Europe]] and elsewhere in the world.<ref name=UKlabel>{{cite web|title=Mianserin 30 mg film-coated tablets|url= https://www.medicines.org.uk/emc/medicine/33601|publisher=UK Electronic Medicines Compendium|access-date=20 August 2017| date= January 2014}}</ref> It is a [[tetracyclic antidepressant]] (TeCA). Mianserin is closely related to [[mirtazapine]], both [[chemical structure |chemically]] and in terms of its actions and effects, although there are significant differences between the two drugs.<ref name=MirtazDiff>{{cite web|title=A Comparison of the Physicochemical and Biological Properties of Mirtazapine and Mianserin |url= https://academic.oup.com/jpp/article/49/4/403/6152885?login=false |publisher = Oxford University Press | work = Journal of pharmacy and pharmacology|access-date=29 January 2022|date= April 2011}}</ref>

==Medical uses==

Mianserin at higher doses (30&ndash;90mg/day) is used for the treatment of [[major depressive disorder]].<ref name=UKlabel/>

It can also be used at lower doses (around 10mg/day) to treat insomnia.<ref>{{cite web | work = Sommeil |url=http://sommeil.univ-lyon1.fr/articles/royant-parola/insomnie/therap.php | trans-title = What to do when facing insomnia | place = [[Lyon]], [[France | FR]] | lang = fr |title = Que faire devant une insomnie | publisher = University of Lyon}}</ref><ref>{{cite web |url= https://www.researchgate.net/publication/242534517 | work = Research gate |url-status= dead | trans-title = Treatment of the troubles of sleep | lang = fr |archive-url= https://web.archive.org/web/20190330221534/https://www.researchgate.net/publication/242534517_Traitement_des_troubles_du_sommeil |archive-date= 2019-03-30 |title=Traitement des troubles du sommeil}}</ref>

==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.<ref name=UKlabel/>

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.<ref name=UKlabel/>

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.<ref name=UKlabel/>

Very common (incidence > 10%) adverse effects include constipation, dry mouth, and drowsiness at the beginning of treatment.<ref name = "TOLVON">{{cite web | title = Tolvon Product Information | work = Medicines | url = http://www.medicines.org.au/files/mkptolvo.pdf | publisher = Merck Sharp & Dohme | place = [[Australia | AU]] | via = GuildLink | access-date = 2013-10-05 | archive-date = 2016-04-02 | archive-url = https://web.archive.org/web/20160402114323/http://www.medicines.org.au//files/mkptolvo.pdf | url-status = dead }}</ref><ref name=UKlabel/>

Common (1% < incidence ≤ 10%) adverse effects include drowsiness during maintenance therapy, tremor, headache, dizziness, vertigo, and weakness.<ref name = "TOLVON"/>

Uncommon (0.1% < incidence ≤ 1%) adverse effects include weight gain.<ref name = "TOLVON"/>

===Withdrawal===

Abrupt or rapid discontinuation of mianserin may provoke a [[Drug withdrawal |withdrawal]], the [[adverse effect|effect]]s of which may include [[Depression (mood)|depression]], [[anxiety]], [[panic attack]]s,<ref name="pmid2796025">{{cite journal | vauthors = Kuniyoshi M, Arikawa K, Miura C, Inanaga K | title = Panic anxiety after abrupt discontinuation of mianserin | journal = The Japanese Journal of Psychiatry and Neurology | volume = 43 | issue = 2 | pages = 155–59 | date = June 1989 | pmid = 2796025 | doi = 10.1111/j.1440-1819.1989.tb02564.x | s2cid = 527031 }}</ref> decreased [[appetite]] or [[Anorexia (symptom)|anorexia]], [[insomnia]], [[diarrhea]], [[nausea]] and [[vomiting]], and [[flu]]-like symptoms, such as [[allergies]] or [[pruritus]], among others.

==Overdose==

Overdose of mianserin is known to produce sedation, coma, hypotension or hypertension, tachycardia, and QT interval prolongation.<ref name = "MPG">{{cite book | vauthors = Taylor D, Paton C, Kapur S, Taylor D | title = The Maudsley Prescribing Guidelines in Psychiatry | edition = 11th | location = Chichester, West Sussex | publisher = John Wiley & Sons | date = 2012 }}</ref>

== Interactions ==

Mianserin may enhance the sedative effects of drugs such as [[alcohol (drug)|alcohol]], anxiolytics, hypnotics, or antipsychotics when co-administered. It may decrease the efficacy of [[antiepileptic]] medications.

[[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 [[antihistamines]] and [[antimuscarinics]] have stronger effects. Mianserin should not be taken with [[apraclonidine]], [[brimonidine]], [[sibutramine]], or the combination drug of [[artemether]] with [[lumefantrine]].<ref name=UKlabel/>

==Pharmacology==

===Pharmacodynamics===

{{See also|Pharmacology of antidepressants|Tetracyclic antidepressant#Pharmacology}}

{| class="wikitable floatright" style="font-size:small;"

|+ Mianserin<ref name="PDSP">{{cite web | title = PDSP K_i Database | work = Psychoactive Drug Screening Program (PDSP)|author1-link=Bryan Roth | vauthors = Roth BL, Driscol J | publisher = University of North Carolina at Chapel Hill and the United States National Institute of Mental Health | access-date = 14 August 2017 | url = https://kidbdev.med.unc.edu/databases/pdsp.php?knowID=0&kiKey=&receptorDD=&receptor=&speciesDD=&species=&sourcesDD=&source=&hotLigandDD=&hotLigand=&testLigandDD=&testFreeRadio=testFreeRadio&testLigand=mianserin&referenceDD=&reference=&KiGreater=&KiLess=&kiAllRadio=all&doQuery=Submit+Query}}</ref>

|-

! Site !! ''K''_i (nM) !! Species !! Ref

|-

| {{abbrlink|SERT|Serotonin transporter}} || 4,000 || Human || <ref name="pmid9537821">{{cite journal | vauthors = Tatsumi M, Groshan K, Blakely RD, Richelson E | title = Pharmacological profile of antidepressants and related compounds at human monoamine transporters | journal = European Journal of Pharmacology | volume = 340 | issue = 2–3 | pages = 249–258 | date = December 1997 | pmid = 9537821 | doi = 10.1016/s0014-2999(97)01393-9 }}</ref>

|-

| {{abbrlink|NET|Norepinephrine transporter}} || 71 || Human || <ref name="pmid9537821" />

|-

| {{abbrlink|DAT|Dopamine transporter}} || 9,400 || Human || <ref name="pmid9537821" />

|-

| [[5-HT1A receptor|5-HT_1A]] || 400–2,600 || Human || <ref name="pmid7984267">{{cite journal | vauthors = Boess FG, Martin IL | title = Molecular biology of 5-HT receptors | journal = Neuropharmacology | volume = 33 | issue = 3–4 | pages = 275–317 | year = 1994 | pmid = 7984267 | doi = 10.1016/0028-3908(94)90059-0 | s2cid = 35553281 }}</ref><ref name="pmid9686407">{{cite journal | vauthors = Toll L, Berzetei-Gurske IP, Polgar WE, Brandt SR, Adapa ID, Rodriguez L, Schwartz RW, Haggart D, O'Brien A, White A, Kennedy JM, Craymer K, Farrington L, Auh JS | display-authors = 6 | title = Standard binding and functional assays related to medications development division testing for potential cocaine and opiate narcotic treatment medications | journal = NIDA Research Monograph | volume = 178 | pages = 440–466 | date = March 1998 | pmid = 9686407 }}</ref>

|-

| [[5-HT1B receptor|5-HT_1B]] || ≥2,800 || Rat || <ref name="pmid1738111">{{cite journal | vauthors = Matsumoto I, Combs MR, Jones DJ | title = Characterization of 5-hydroxytryptamine1B receptors in rat spinal cord via [125I]iodocyanopindolol binding and inhibition of [3H]-5-hydroxytryptamine release | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 260 | issue = 2 | pages = 614–626 | date = February 1992 | pmid = 1738111 }}</ref>

|-

| [[5-HT1D receptor|5-HT_1D]] || 220–400 || Human || <ref name="pmid2521959">{{cite journal | vauthors = Peroutka SJ, Switzer JA, Hamik A | title = Identification of 5-hydroxytryptamine1D binding sites in human brain membranes | journal = Synapse | volume = 3 | issue = 1 | pages = 61–66 | year = 1989 | pmid = 2521959 | doi = 10.1002/syn.890030109 | s2cid = 23503235 }}</ref><ref name="pmid2975354">{{cite journal | vauthors = Waeber C, Schoeffter P, Palacios JM, Hoyer D | title = Molecular pharmacology of 5-HT1D recognition sites: radioligand binding studies in human, pig and calf brain membranes | journal = Naunyn-Schmiedeberg's Archives of Pharmacology | volume = 337 | issue = 6 | pages = 595–601 | date = June 1988 | pmid = 2975354 | doi = 10.1007/bf00175783 | s2cid = 21344978 }}</ref>

|-

| [[5-HT1E receptor|5-HT_1E]] || {{abbr|ND|No data}} || {{abbr|ND|No data}} || {{abbr|ND|No data}}

|-

| [[5-HT1F receptor|5-HT_1F]] || 13 || Human || <ref name="pmid7984267" />

|-

| [[5-HT2A receptor|5-HT_2A]] || 1.6–55 || Human || <ref name="pmid10611634">{{cite journal | vauthors = Millan MJ, Newman-Tancredi A, Audinot V, Cussac D, Lejeune F, Nicolas JP, Cogé F, Galizzi JP, Boutin JA, Rivet JM, Dekeyne A, Gobert A | display-authors = 6 | title = Agonist and antagonist actions of yohimbine as compared to fluparoxan at alpha(2)-adrenergic receptors (AR)s, serotonin (5-HT)(1A), 5-HT(1B), 5-HT(1D) and dopamine D(2) and D(3) receptors. Significance for the modulation of frontocortical monoaminergic transmission and depressive states | journal = Synapse | volume = 35 | issue = 2 | pages = 79–95 | date = February 2000 | pmid = 10611634 | doi = 10.1002/(SICI)1098-2396(200002)35:2<79::AID-SYN1>3.0.CO;2-X | s2cid = 20221398 }}</ref><ref name="pmid2723656">{{cite journal | vauthors = Elliott JM, Kent A | title = Comparison of [125I]iodolysergic acid diethylamide binding in human frontal cortex and platelet tissue | journal = Journal of Neurochemistry | volume = 53 | issue = 1 | pages = 191–196 | date = July 1989 | pmid = 2723656 | doi = 10.1111/j.1471-4159.1989.tb07313.x | s2cid = 25820829 }}</ref>

|-

| [[5-HT2B receptor|5-HT_2B]] || 1.6–20 || Human || <ref name="pmid10455251">{{cite journal | vauthors = Bonhaus DW, Flippin LA, Greenhouse RJ, Jaime S, Rocha C, Dawson M, Van Natta K, Chang LK, Pulido-Rios T, Webber A, Leung E, Eglen RM, Martin GR | display-authors = 6 | title = RS-127445: a selective, high affinity, orally bioavailable 5-HT2B receptor antagonist | journal = British Journal of Pharmacology | volume = 127 | issue = 5 | pages = 1075–1082 | date = July 1999 | pmid = 10455251 | pmc = 1566110 | doi = 10.1038/sj.bjp.0702632 }}</ref><ref name="pmid7582481">{{cite journal | vauthors = Bonhaus DW, Bach C, DeSouza A, Salazar FH, Matsuoka BD, Zuppan P, Chan HW, Eglen RM | display-authors = 6 | title = The pharmacology and distribution of human 5-hydroxytryptamine2B (5-HT2B) receptor gene products: comparison with 5-HT2A and 5-HT2C receptors | journal = British Journal of Pharmacology | volume = 115 | issue = 4 | pages = 622–628 | date = June 1995 | pmid = 7582481 | pmc = 1908489 | doi = 10.1111/j.1476-5381.1995.tb14977.x }}</ref>

|-

| [[5-HT2C receptor|5-HT_2C]] || 0.63–6.5 || Human || <ref name="pmid10611634" /><ref name="pmid8632342">{{cite journal | vauthors = Wainscott DB, Lucaites VL, Kursar JD, Baez M, Nelson DL | title = Pharmacologic characterization of the human 5-hydroxytryptamine2B receptor: evidence for species differences | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 276 | issue = 2 | pages = 720–727 | date = February 1996 | pmid = 8632342 }}</ref>

|-

| [[5-HT3 receptor|5-HT₃]] || 5.8–300 || Rodent || <ref name="pmid2543418">{{cite journal | vauthors = Nelson DR, Thomas DR | title = [3H]-BRL 43694 (Granisetron), a specific ligand for 5-HT3 binding sites in rat brain cortical membranes | journal = Biochemical Pharmacology | volume = 38 | issue = 10 | pages = 1693–1695 | date = May 1989 | pmid = 2543418 | doi = 10.1016/0006-2952(89)90319-5 }}</ref><ref name="pmid9686407" />

|-

| [[5-HT4 receptor|5-HT₄]] || {{abbr|ND|No data}} || {{abbr|ND|No data}} || {{abbr|ND|No data}}

|-

| [[5-HT5A receptor|5-HT_5A]] || {{abbr|ND|No data}} || {{abbr|ND|No data}} || {{abbr|ND|No data}}

|-

| [[5-HT6 receptor|5-HT₆]] || 55–81 || Human || <ref name="pmid8522988">{{cite journal | vauthors = Kohen R, Metcalf MA, Khan N, Druck T, Huebner K, Lachowicz JE, Meltzer HY, Sibley DR, Roth BL, Hamblin MW | display-authors = 6 | title = Cloning, characterization, and chromosomal localization of a human 5-HT6 serotonin receptor | journal = Journal of Neurochemistry | volume = 66 | issue = 1 | pages = 47–56 | date = January 1996 | pmid = 8522988 | doi = 10.1046/j.1471-4159.1996.66010047.x | s2cid = 35874409 }}</ref><ref name="pmid14645659">{{cite journal | vauthors = Hirst WD, Abrahamsen B, Blaney FE, Calver AR, Aloj L, Price GW, Medhurst AD | title = Differences in the central nervous system distribution and pharmacology of the mouse 5-hydroxytryptamine-6 receptor compared with rat and human receptors investigated by radioligand binding, site-directed mutagenesis, and molecular modeling | journal = Molecular Pharmacology | volume = 64 | issue = 6 | pages = 1295–1308 | date = December 2003 | pmid = 14645659 | doi = 10.1124/mol.64.6.1295 }}</ref>

|-

| [[5-HT7 receptor|5-HT₇]] || 48–56 || Human || <ref name="pmid15771415">{{cite journal | vauthors = Fernández J, Alonso JM, Andrés JI, Cid JM, Díaz A, Iturrino L, Gil P, Megens A, Sipido VK, Trabanco AA | display-authors = 6 | title = Discovery of new tetracyclic tetrahydrofuran derivatives as potential broad-spectrum psychotropic agents | journal = Journal of Medicinal Chemistry | volume = 48 | issue = 6 | pages = 1709–1712 | date = March 2005 | pmid = 15771415 | doi = 10.1021/jm049632c }}</ref><ref name="pmid9298538">{{cite journal | vauthors = Jasper JR, Kosaka A, To ZP, Chang DJ, Eglen RM | title = Cloning, expression and pharmacology of a truncated splice variant of the human 5-HT7 receptor (h5-HT7b) | journal = British Journal of Pharmacology | volume = 122 | issue = 1 | pages = 126–132 | date = September 1997 | pmid = 9298538 | pmc = 1564895 | doi = 10.1038/sj.bjp.0701336 }}</ref><ref name="pmid9149537">{{cite journal | vauthors = Eglen RM, Jasper JR, Chang DJ, Martin GR | title = The 5-HT7 receptor: orphan found | journal = Trends in Pharmacological Sciences | volume = 18 | issue = 4 | pages = 104–107 | date = April 1997 | pmid = 9149537 | doi = 10.1016/s0165-6147(97)01043-2 }}</ref>

|-

| [[Alpha-1 adrenergic receptor|α₁]] || 34 || Human || <ref name="pmid6086881">{{cite journal | vauthors = Richelson E, Nelson A | title = Antagonism by antidepressants of neurotransmitter receptors of normal human brain in vitro | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 230 | issue = 1 | pages = 94–102 | date = July 1984 | pmid = 6086881 }}</ref>

|-

| [[Alpha-2 adrenergic receptor|α₂]] || 73 || Human || <ref name="pmid6086881" />

|-

| &nbsp;&nbsp;[[Alpha-2A adrenergic receptor|α_2A]] || 4.8 || Human || <ref name="pmid15771415" />

|-

| &nbsp;&nbsp;[[Alpha-2B adrenergic receptor|α_2B]] || 27 || Human || <ref name="pmid2172775">{{cite journal | vauthors = Weinshank RL, Zgombick JM, Macchi M, Adham N, Lichtblau H, Branchek TA, Hartig PR | title = Cloning, expression, and pharmacological characterization of a human alpha 2B-adrenergic receptor | journal = Molecular Pharmacology | volume = 38 | issue = 5 | pages = 681–688 | date = November 1990 | pmid = 2172775 }}</ref>

|-

| &nbsp;&nbsp;[[Alpha-2C adrenergic receptor|α_2C]] || 3.8 || Human || <ref name="pmid15771415" />

|-

| [[Dopamine D1 receptor|D₁]] || 426–1,420 || Human || <ref name="pmid9686407" /><ref name="pmid15771415" />

|-

| [[Dopamine D2 receptor|D₂]] || 2,100–2,700 || Human || <ref name="pmid6086881" /><ref name="pmid2532362">{{cite journal | vauthors = Grandy DK, Marchionni MA, Makam H, Stofko RE, Alfano M, Frothingham L, Fischer JB, Burke-Howie KJ, Bunzow JR, Server AC | display-authors = 6 | title = Cloning of the cDNA and gene for a human D2 dopamine receptor | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 86 | issue = 24 | pages = 9762–9766 | date = December 1989 | pmid = 2532362 | pmc = 298581 | doi = 10.1073/pnas.86.24.9762 | doi-access = free | bibcode = 1989PNAS...86.9762G }}</ref>

|-

| [[Dopamine D3 receptor|D₃]] || 2,840 || Human || <ref name="pmid6086881" />

|-

| [[Dopamine D4 receptor|D₄]] || {{abbr|ND|No data}} || {{abbr|ND|No data}} || {{abbr|ND|No data}}

|-

| [[Dopamine D5 receptor|D₅]] || {{abbr|ND|No data}} || {{abbr|ND|No data}} || {{abbr|ND|No data}}

|-

| [[Histamine H1 receptor|H₁]] || 0.30–1.7 || Human || <ref name="pmid16782354">{{cite journal | vauthors = Ghoneim OM, Legere JA, Golbraikh A, Tropsha A, Booth RG | title = Novel ligands for the human histamine H1 receptor: synthesis, pharmacology, and comparative molecular field analysis studies of 2-dimethylamino-5-(6)-phenyl-1,2,3,4-tetrahydronaphthalenes | journal = Bioorganic & Medicinal Chemistry | volume = 14 | issue = 19 | pages = 6640–6658 | date = October 2006 | pmid = 16782354 | doi = 10.1016/j.bmc.2006.05.077 }}</ref><ref name="pmid6086881" /><ref name="pmid15771415" />

|-

| [[Histamine H2 receptor|H₂]] || 437 || Human || <ref name="pmid22033803">{{cite journal | vauthors = Appl H, Holzammer T, Dove S, Haen E, Strasser A, Seifert R | title = Interactions of recombinant human histamine H₁R, H₂R, H₃R, and H₄R receptors with 34 antidepressants and antipsychotics | journal = Naunyn-Schmiedeberg's Archives of Pharmacology | volume = 385 | issue = 2 | pages = 145–170 | date = February 2012 | pmid = 22033803 | doi = 10.1007/s00210-011-0704-0 | s2cid = 14274150 }}</ref>

|-

| [[Histamine H3 receptor|H₃]] || 95,500 || Human || <ref name="pmid22033803" />

|-

| [[Histamine H4 receptor|H₄]] || >100,000 || Human || <ref name="pmid22033803" /><ref name="pmid11179435">{{cite journal | vauthors = Nguyen T, Shapiro DA, George SR, Setola V, Lee DK, Cheng R, Rauser L, Lee SP, Lynch KR, Roth BL, O'Dowd BF | display-authors = 6 | title = Discovery of a novel member of the histamine receptor family | journal = Molecular Pharmacology | volume = 59 | issue = 3 | pages = 427–433 | date = March 2001 | pmid = 11179435 | doi = 10.1124/mol.59.3.427 | url = https://cdr.lib.unc.edu/downloads/8336h388z }}</ref>

|-

| {{abbrlink|mACh|Muscarinic acetylcholine receptor}} || 820 || Human || <ref name="pmid6086881" />

|-

| {{abbrlink|MOR|μ-Opioid receptor}} || 21,000 || Human || <ref name="pmid22708686">{{cite journal | vauthors = Olianas MC, Dedoni S, Onali P | title = The atypical antidepressant mianserin exhibits agonist activity at κ-opioid receptors | journal = British Journal of Pharmacology | volume = 167 | issue = 6 | pages = 1329–1341 | date = November 2012 | pmid = 22708686 | pmc = 3504997 | doi = 10.1111/j.1476-5381.2012.02078.x }}</ref>

|-

| {{abbrlink|DOR|δ-Opioid receptor}} || 30,200 || Human || <ref name="pmid22708686" />

|-

| {{abbrlink|KOR|κ-Opioid receptor}} || 530 ({{abbrlink|EC₅₀|Half-maximal effective concentration}}) || Human || <ref name="pmid22708686" />

|- class="sortbottom"

| colspan="4" style="width: 1px;" | Values are K_i (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 [[histamine]] and [[serotonin]] receptors, and inhibition of [[norepinephrine]] reuptake. More specifically, it is an [[receptor antagonist|antagonist]]/[[inverse agonist]] at most or all sites of the [[histamine]] [[H1 receptor|H₁ receptor]], [[serotonin]] [[5-HT1D|5-HT_1D]], [[5-HT1F|5-HT_1F]], [[5-HT2A|5-HT_2A]], [[5-HT2B|5-HT_2B]], [[5-HT2C|5-HT_2C]], [[5-HT3|5-HT₃]], [[5-HT6|5-HT₆]], and [[5-HT7|5-HT₇ receptor]]s, and adrenergic [[alpha-1 adrenergic receptor|α₁-]] and [[alpha-2 adrenergic receptor|α₂-adrenergic receptor]]s, and additionally a [[norepinephrine]] [[reuptake inhibitor]].<ref name="bookchizophrenia and Mood Disorders: The New Drug Therapies in Clinical Practice">{{cite book |vauthors=Leonard B, Richelson H |veditors=Buckley JL, Waddington PF | title = Schizophrenia and Mood Disorders: The New Drug Therapies in Clinical Practice |url=https://archive.org/details/schizophreniamoo00buck |url-access=limited | year = 2000 | publisher = Butterworth-Heinemann | location = Oxford | isbn = 978-0-7506-4096-1 | chapter = Synaptic Effects of Antidepressants: Relationship to Their Therapeutic and Adverse Effects | pages = [https://archive.org/details/schizophreniamoo00buck/page/n81 67]–84 }}</ref><ref name="KubinyiMüller2006">{{cite book |veditors=Kubinyi H, Müller G, Mannhold R, Folkers G | title = Chemogenomics in Drug Discovery: A Medicinal Chemistry Perspective | vauthors = Müller G | chapter = Target Family-directed Masterkeys in Chemogenomics | chapter-url = https://books.google.com/books?id=oxvYXJSCImUC&pg=PA25 | date = 8 May 2006 | publisher = John Wiley & Sons | isbn = 978-3-527-60402-9 | page = 25}}</ref> As an H₁ receptor inverse agonist with high [[affinity (pharmacology)|affinity]], mianserin has strong [[antihistamine]] effects (e.g., [[sedation]]). Conversely, it has low affinity for the [[muscarinic acetylcholine receptor]]s, and hence lacks [[anticholinergic]] properties.<ref name="pmid6086881" /> Mianserin has been found to be a low affinity but potentially significant [[partial agonist]] of the [[κ-opioid receptor]] (K_i = 1.7&nbsp;μM; [[EC50|EC₅₀]] = 0.53&nbsp;μM),<ref name="pmid22708686" /> similarly to some [[tricyclic antidepressant]]s (TCAs).<ref name="pmid19828880">{{cite journal | vauthors = Onali P, Dedoni S, Olianas MC | title = Direct agonist activity of tricyclic antidepressants at distinct opioid receptor subtypes | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 332 | issue = 1 | pages = 255–265 | date = January 2010 | pmid = 19828880 | doi = 10.1124/jpet.109.159939 | s2cid = 18893305 }}</ref>

Blockade of the H₁ and possibly α₁-adrenergic receptors has [[sedative]] effects,<ref name = "TOLVON"/> and also antagonism of the 5-HT_2A and α₁-adrenergic receptors inhibits activation of [[intracellular]] [[phospholipase C]] (PLC), which seems to be a common target for several different [[chemical classification|class]]es of [[antidepressant]]s.<ref name="pmid12527476">{{cite journal | vauthors = Dwivedi Y, Agrawal AK, Rizavi HS, Pandey GN | title = Antidepressants reduce phosphoinositide-specific phospholipase C (PI-PLC) activity and the mRNA and protein expression of selective PLC beta 1 isozyme in rat brain | journal = Neuropharmacology | volume = 43 | issue = 8 | pages = 1269–1279 | date = December 2002 | pmid = 12527476 | doi = 10.1016/S0028-3908(02)00253-8 | s2cid = 22105260 }}</ref> By antagonizing the [[somatodendritic]] and [[presynaptic]] α₂-adrenergic receptors, which function predominantly as [[IPSP|inhibitory]] [[autoreceptor]]s and [[heteroreceptor]]s, mianserin disinhibits the release of [[norepinephrine]], [[dopamine]], [[serotonin]], and [[acetylcholine]] in various areas of the [[brain]] and [[Human body|body]].

Along with mirtazapine, although to a lesser extent in comparison, mianserin has sometimes been described as a [[noradrenergic and specific serotonergic antidepressant]] (NaSSA).<ref name="pmid23823741">{{cite journal | vauthors = Kishi T, Iwata N | title = Meta-analysis of noradrenergic and specific serotonergic antidepressant use in schizophrenia | journal = The International Journal of Neuropsychopharmacology | volume = 17 | issue = 2 | pages = 343–354 | date = February 2014 | pmid = 23823741 | doi = 10.1017/S1461145713000667 | doi-access = free }}</ref> However, the actual evidence in support of this label has been regarded as poor.<ref name="pmid16342227">{{cite journal | vauthors = Gillman PK | title = A systematic review of the serotonergic effects of mirtazapine in humans: implications for its dual action status | journal = Human Psychopharmacology | volume = 21 | issue = 2 | pages = 117–125 | date = March 2006 | pmid = 16342227 | doi = 10.1002/hup.750 | s2cid = 23442056 }}</ref>

===Pharmacokinetics===

The [[bioavailability]] of mianserin is 20 to 30%.<ref name="DD" /> Its [[plasma protein binding]] is 95%.<ref name="DD" /> Mianserin is [[metabolism|metabolized]] in the [[liver]] by the [[CYP2D6]] [[enzyme]] via ''N''-[[oxidation]] and ''N''-[[demethylation]].<ref name="DD" /> Its [[elimination half-life]] is 21 to 61 hours.<ref name="DD" /> The drug is [[excretion|excreted]] 4 to 7% in the [[urine]] and 14 to 28% in [[feces]].<ref name="DD" />

==Chemistry==

[[File:Esmianserin.svg|thumb|left|175px|(''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.<ref>{{cite web|title= Mirtazapine label &ndash; Australia|url= http://secure.healthlinks.net.au/content/msd/pi.cfm?product=mkpavant|publisher= GuildLink, Pharmacy Guild of Australia|date= 27 May 2016|access-date= 21 June 2017|archive-date= 21 November 2018|archive-url= https://web.archive.org/web/20181121120001/http://secure.healthlinks.net.au/content/msd/pi.cfm?product=mkpavant|url-status= dead}}</ref><ref>{{cite journal | vauthors = Kelder J, Funke C, De Boer T, Delbressine L, Leysen D, Nickolson V | title = A comparison of the physicochemical and biological properties of mirtazapine and mianserin | journal = The Journal of Pharmacy and Pharmacology | volume = 49 | issue = 4 | pages = 403–11 | date = April 1997 | pmid = 9232538 | doi = 10.1111/j.2042-7158.1997.tb06814.x | s2cid = 12270528| doi-access = free }}</ref> (''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|date=October 2013}}

==History==

It was [[drug development|developed]] but not discovered by [[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.<ref>{{cite book | vauthors = Shorter E |title=A historical dictionary of psychiatry |date=2005|publisher=Oxford Univ. Press|location=Oxford |isbn= 978-0-19-517668-1}}</ref>{{rp|21}}<ref name=Stahl4th>{{cite book | vauthors = Stahl SM |title=Stahl's essential psychopharmacology : neuroscientific basis and practical application |date= 2013|publisher=Cambridge University Press |location= Cambridge |isbn= 978-1-10702598-1|edition=4th}}</ref>{{rp |318}}

Mianserin was one of the first antidepressants to reach the UK market that was less dangerous than the [[tricyclic antidepressant]]s in overdose; as of 2012 it was not prescribed much in the UK.<ref>{{cite book| vauthors = Pratt JP | veditors = Walker R, Whittlesea C |title=Clinical pharmacy and therapeutics |date= 2012 |publisher=Churchill Livingston/Elsevier|location= Edinburgh |isbn= 978-0-70204293-5|page=472|edition=5th|chapter=29. Affective Disorders}}</ref>

==Society and culture==

[[File:Mianserin.JPG|thumb|left|Mianserin.]]

===Generic names===

''Mianserin'' is the [[English language|English]] and [[German language|German]] [[generic term|generic name]] of the drug and its {{abbrlink|INN|International Nonproprietary Name}} and {{abbrlink|BAN|British Approved Name}}, while ''mianserin hydrochloride'' is its {{abbrlink|USAN|United States Adopted Name}}, {{abbrlink|BANM|British Approved Name}}, and {{abbrlink|JAN|Japanese Accepted Name}}. Its generic name in [[French language|French]] and its {{abbrlink|DCF|Dénomination Commune Française}} are ''miansérine'', in [[Spanish language|Spanish]] and [[Italian language|Italian]] and its {{abbrlink|DCIT|Denominazione Comune Italiana}} are ''mianserina'', and in [[Latin language|Latin]] is ''mianserinum''.<ref name="Elks2014">{{cite book| vauthors = Elks J |title=The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies|url=https://books.google.com/books?id=0vXTBwAAQBAJ&pg=PA822|date=14 November 2014|publisher=Springer|isbn=978-1-4757-2085-3|pages=822–}}</ref><ref name="IndexNominum2000">{{cite book|title=Index Nominum 2000: International Drug Directory|url=https://books.google.com/books?id=5GpcTQD_L2oC&pg=PA689|year=2000|publisher=Taylor & Francis|isbn=978-3-88763-075-1|pages=689–}}</ref><ref name="MortonHall1999">{{cite book| vauthors = Morton IK, Hall JM |title=Concise Dictionary of Pharmacological Agents: Properties and Synonyms|url=https://books.google.com/books?id=mqaOMOtk61IC&pg=PA181|date=31 October 1999|publisher=Springer Science & Business Media|isbn=978-0-7514-0499-9|pages=181–}}</ref><ref name="Drugs.com">{{cite web|title=International brands for mianserin|url=https://www.drugs.com/international/mianserin.html|publisher=Drugs.com|access-date=20 August 2017}}</ref>

===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.<ref name="IndexNominum2000" /><ref name="Drugs.com" /><ref name="Elks2014" />

===Availability===

Mianserin is not approved for use in the [[United States]], but is available in the [[United Kingdom]] and other [[Europe]]an countries.<ref name= "GelenbergBassuk2013">{{cite book | vauthors = Gelenberg AJ, Schoonover SC | chapter = Major Psychiatric Disorders: Depression | veditors = Gelenberg AJ, Bassuk EL, Schoonover SC |title= The Practitioner's Guide to Psychoactive Drugs | chapter-url= https://books.google.com/books?id=4nzSBwAAQBAJ&pg=PA39 |date= 29 June 2013 |publisher=Springer Science & Business Media |isbn= 978-1-4757-1137-0 |pages=39–}}</ref><ref name="KleinRowland2013">{{cite book | vauthors = Quitkin FM, Taylor BP | chapter = Antidepressants | veditors = Klein DF, Rowland LP |title= Current Psychotherapeutic Drugs | chapter-url = https://books.google.com/books?id=rc9mVkQbJlMC&pg=PT57 |date=24 May 2013 |publisher=Routledge|isbn= 978-1-135-06284-2 |pages= 57–}}</ref> A mianserin generic drug received {{abbrlink |TGA|Therapeutic Goods Administration}} approval in May 1996 and is available in [[Australia]].<ref name = "LUMIN">{{cite web | title = Lumin Mianserin hydrochloride product information | work = Medicines | url = http://www.medicines.org.au/files/afplumin.pdf | publisher = AlphaPharm | via = GuildLink}}</ref>

==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.<ref>{{cite journal | vauthors = Terevnikov V, Joffe G, Stenberg JH | title = Randomized Controlled Trials of Add-On Antidepressants in Schizophrenia | journal = The International Journal of Neuropsychopharmacology | volume = 18 | issue = 9 | page = pyv049 | date = May 2015 | pmid = 25991654 | pmc = 4576515 | doi = 10.1093/ijnp/pyv049 }}</ref><ref>{{cite journal | vauthors = Vernon JA, Grudnikoff E, Seidman AJ, Frazier TW, Vemulapalli MS, Pareek P, Goldberg TE, Kane JM, Correll CU | display-authors = 6 | title = Antidepressants for cognitive impairment in schizophrenia--a systematic review and meta-analysis | journal = Schizophrenia Research | volume = 159 | issue = 2–3 | pages = 385–394 | date = November 2014 | pmid = 25240772 | pmc = 4252251 | doi = 10.1016/j.schres.2014.08.015 }}</ref>

== References ==

{{Reflist}}

== Further reading ==

{{refbegin}}

* {{cite journal | vauthors = Peet M, Behagel H | title = Mianserin: a decade of scientific development | journal = British Journal of Clinical Pharmacology | volume = 5 | issue = Suppl 1 | pages = 5S–9S | year = 1978 | doi = 10.1111/j.1365-2125.1978.tb04567.x | pmid = 623702 | pmc = 1429213 }}

{{refend}}

{{Navboxes

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[[Category:5-HT1F antagonists]]

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