Cyamemazine

{{Short description|Antipsychotic medication}} {{cs1 config|name-list-style=vanc}} {{Drugbox | Verifiedfields = changed | Watchedfields = changed | verifiedrevid = 444653764 | IUPAC_name = 10-(3-dimethylamino-2-methyl-propyl)phenothiazine-2-carbonitrile | image = Cyamemazine.svg | image_class = skin-invert-image

<!--Clinical data--> | tradename = Tercian | Drugs.com = {{drugs.com|international|cyamemazine}} | pregnancy_category = | legal_status = Rx-Only | routes_of_administration = Oral, IM, IV

<!--Pharmacokinetic data--> | bioavailability = 10-70% | protein_bound = | metabolism = Hepatic | elimination_half-life = 10 hours | excretion = Urine

<!--Identifiers--> | CAS_number_Ref = {{cascite|correct|??}} | CAS_number = 3546-03-0 | ATC_prefix = N05 | ATC_suffix = AA06 | PubChem = 62865 | IUPHAR_ligand = 84 | DrugBank_Ref = {{drugbankcite|changed|drugbank}} | DrugBank = DB09000 | ChEMBL_Ref = {{ebicite|changed|EBI}} | ChEMBL = 2104153 | ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} | ChemSpiderID = 56597 | UNII_Ref = {{fdacite|correct|FDA}} | UNII = A2JGV5CNU4 | KEGG_Ref = {{keggcite|correct|kegg}} | KEGG = D07307

<!--Chemical data--> | C=19 | H=21 | N=3 | S=1 | smiles = N#Cc2cc1N(c3c(Sc1cc2)cccc3)CC(C)CN(C)C | StdInChI_Ref = {{stdinchicite|correct|chemspider}} | StdInChI = 1S/C19H21N3S/c1-14(12-21(2)3)13-22-16-6-4-5-7-18(16)23-19-9-8-15(11-20)10-17(19)22/h4-10,14H,12-13H2,1-3H3 | StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} | StdInChIKey = SLFGIOIONGJGRT-UHFFFAOYSA-N }}

'''Cyamemazine''' ('''Tercian'''), also known as '''cyamepromazine''', is a typical antipsychotic drug of the phenothiazine class which was introduced by Theraplix in France in 1972 and later in Portugal as well.<ref name="urlIndex nominum, international drug ... - Google Books">{{cite book | url = https://books.google.com/books?id=5GpcTQD_L2oC&q=cyamemazine%20tercian&pg=PA280 | title = Index Nominum, International Drug | publisher = Taylor & Francis | isbn = 978-3-88763-075-1 | year = 2000 }}</ref><ref name="isbn0-412-46630-9">{{cite book | vauthors = Triggle DJ | title = Dictionary of Pharmacological Agents | publisher = Chapman & Hall/CRC | location = Boca Raton | year = 1996 | page = 534 | isbn = 0-412-46630-9 | url = https://books.google.com/books?id=DeX7jgInYFMC&pg=RA1-PA534}}</ref><ref name="urlPharmaceutical manufacturing ... - Google Books">{{cite book | url = https://books.google.com/books?id=X2EyLsG4bcUC&q=cyamemazine%20introduced&pg=PA397 | title = Pharmaceutical manufacturing ... - Google Books | isbn = 9780815511441 | vauthors = Sittig M | date = January 1988 | publisher = Noyes Publications }}</ref><ref name="pmid19393381">{{cite journal | vauthors = Bret P, Bret MC, Queuille E | title = [Prescribing patterns of antipsychotics in 13 French psychiatric hospitals] | language = fr | journal = L'Encephale | volume = 35 | issue = 2 | pages = 129–138 | date = April 2009 | pmid = 19393381 | doi = 10.1016/j.encep.2008.03.007 | url = http://www.masson.fr/masson/S0013-7006(08)00103-6 | url-status = dead | archive-url = https://archive.today/20130213173522/http://www.masson.fr/masson/S0013-7006(08)00103-6 | archive-date = 2013-02-13 | url-access = subscription }}</ref>

==Medical use== It is used for the treatment of schizophrenia and, especially, for psychosis-associated anxiety, due to its unique anxiolytic efficacy.<ref name="urlStahls Essential Psychopharmacology - Cambridge University Press">{{cite book | chapter-url = http://stahlonline.cambridge.org/prescribers_drug.jsf?page=0521683505c20_p115-120.html.therapeutics&name=Cyamemazine | chapter = Cyamemazine | title = Stahl's Essential Psychopharmacology | publisher = Cambridge University Press }}</ref><ref name="pmid11423169">{{cite journal | vauthors = Bourin M, Claude Colombel M, Dib M, Hascoët M | title = Cyamemazine as an anxiolytic drug on the elevated plus maze and light/dark paradigm in mice | journal = Behavioural Brain Research | volume = 124 | issue = 1 | pages = 87–95 | date = September 2001 | pmid = 11423169 | doi = 10.1016/S0166-4328(01)00238-8 | s2cid = 43312295 }}</ref>

It is also used to reduce anxiety associated with benzodiazepine withdrawal syndrome and anxiety in depression with suicidal tendency.<ref name="Benyamina Naassila Bourin 2012 pp. 307–312">{{cite journal | vauthors = Benyamina A, Naassila M, Bourin M | title = Potential role of cortical 5-HT(2A) receptors in the anxiolytic action of cyamemazine in benzodiazepine withdrawal | journal = Psychiatry Research | volume = 198 | issue = 2 | pages = 307–312 | date = July 2012 | pmid = 22421069 | doi = 10.1016/j.psychres.2012.01.009 | publisher = Elsevier BV | s2cid = 34830082 }}</ref>

==Side effects== Here are some of the most common side effects and related incidence:<ref name="Bourin Dailly Hascöet pp. 219–229">{{cite journal | vauthors = Bourin M, Dailly E, Hascöet M | title = Preclinical and clinical pharmacology of cyamemazine: anxiolytic effects and prevention of alcohol and benzodiazepine withdrawal syndrome | journal = CNS Drug Reviews | volume = 10 | issue = 3 | pages = 219–229 | date = 2006-06-07 | pmid = 15492772 | pmc = 6741725 | doi = 10.1111/j.1527-3458.2004.tb00023.x | publisher = Wiley }}</ref> * Sedation (20%) * Vertigo (7.9%) * Constipation (4%) * Dyskinesia (4.4%) * Dryness of mouth (5.9%) * Hypotension (7.4%) * Tachycardia (3.2%)

==Mechanism== Cyamemazine differs from other phenothiazine neuroleptics in that aside from the usual profile of dopamine, α₁-adrenergic, H₁, and mACh receptor antagonism,<ref name="pmid12527336">{{cite journal | vauthors = Hameg A, Bayle F, Nuss P, Dupuis P, Garay RP, Dib M | title = Affinity of cyamemazine, an anxiolytic antipsychotic drug, for human recombinant dopamine vs. serotonin receptor subtypes | journal = Biochemical Pharmacology | volume = 65 | issue = 3 | pages = 435–440 | date = February 2003 | pmid = 12527336 | doi = 10.1016/S0006-2952(02)01515-0 }}</ref> it additionally produces potent blockade of several serotonin receptors, including 5-HT_2A, 5-HT_2C, and 5-HT₇.<ref name="pmid12527336"/><ref name="pmid10672635">{{cite journal | vauthors = Alvarez-Guerra M, d'Alché-Birée F, Wolf WA, Vargas F, Dib M, Garay RP | title = 5-HT3- and 5-HT2C-antagonist properties of cyamemazine: significance for its clinical anxiolytic activity | journal = Psychopharmacology | volume = 147 | issue = 4 | pages = 412–417 | date = January 2000 | pmid = 10672635 | doi = 10.1007/s002130050010 | url = http://link.springer.de/link/service/journals/00213/bibs/0147004/01470412.htm | access-date = 2010-02-11 | url-status = dead | s2cid = 25162849 | archive-url = https://web.archive.org/web/20020112021448/http://link.springer.de/link/service/journals/00213/bibs/0147004/01470412.htm | archive-date = 2002-01-12 | url-access = subscription }}</ref><ref name="pmid12421652">{{cite journal | vauthors = Alvarez-Guerra M, Hameg A, Bayle F, Dib M, Garay RP | title = 5-HT2A receptor antagonist properties of cyamemazine in rat and guinea pig smooth muscle | journal = European Journal of Pharmacology | volume = 454 | issue = 2–3 | pages = 235–239 | date = November 2002 | pmid = 12421652 | doi = 10.1016/S0014-2999(02)02489-5 }}</ref><ref name="pmid17936750">{{cite journal | vauthors = Benyamina A, Arbus C, Nuss P, Garay RP, Neliat G, Hameg A | title = Affinity of cyamemazine metabolites for serotonin, histamine and dopamine receptor subtypes | journal = European Journal of Pharmacology | volume = 578 | issue = 2–3 | pages = 142–147 | date = January 2008 | pmid = 17936750 | doi = 10.1016/j.ejphar.2007.09.025 }}</ref> These actions have been implicated in cyamemazine's anxiolytic effects (5-HT_2C) and lack of extrapyramidal side effects (5-HT_2A),<ref name="pmid12527336"/><ref name="pmid10672635"/> and despite being classified as a typical antipsychotic, it actually behaves like an atypical antipsychotic.<ref name="pmid12595954">{{cite journal | vauthors = Peinado J, Hameg A, Garay RP, Bayle F, Nuss P, Dib M | title = Reduction of extracellular dopamine and metabolite concentrations in rat striatum by low doses of acute cyamemazine | journal = Naunyn-Schmiedeberg's Archives of Pharmacology | volume = 367 | issue = 2 | pages = 134–139 | date = February 2003 | pmid = 12595954 | doi = 10.1007/s00210-002-0665-4 | s2cid = 682064 }}</ref> {| class="wikitable sortable floatright" style="font-size:small;" !Site !K_i (nM) !Species !Ref |- |H₁ |9.3 |Guinea pig |<ref name=":0">{{cite journal | vauthors = Hameg A, Bayle F, Nuss P, Dupuis P, Garay RP, Dib M | title = Affinity of cyamemazine, an anxiolytic antipsychotic drug, for human recombinant dopamine vs. serotonin receptor subtypes | journal = Biochemical Pharmacology | volume = 65 | issue = 3 | pages = 435–440 | date = February 2003 | pmid = 12527336 | doi = 10.1016/s0006-2952(02)01515-0 }}</ref> |- |H₂ |351 |Guinea pig |<ref name=":0" /> |- |H₃ |10000+ |Rat |<ref name=":0" /> |- |M₁ |13 |Human |<ref name=":0" /> |- |M₂ |42 |Human |<ref name=":0" /> |- |M₃ |32 |Human |<ref name=":0" /> |- |M₄ |12 |Human |<ref name=":0" /> |- |M₅ |35 |Human |<ref name=":0" /> |- |5-HT_1A |517 |Human |<ref name=":0" /> |- |5-HT_2A |1.5 |Human |<ref name=":0" /> |- |5-HT_2C |12 |Human |<ref name=":0" /> |- |5-HT₃ |2943 |Human |<ref name=":0" /> |- |5-HT₇ |22 |Human |<ref name=":0" /> |- |D₁ |3.8 |Human |<ref name=":0" /> |- |D₂ |5.8 |Human |<ref name=":0" /> |- |D₃ |2.5 |Human |<ref name=":0" /> |- |D₄ |5.3 |Human |<ref name=":0" /> |- |α₁ |2.3 |Rat |<ref name=":0" /> |- |α₂ |1320 |Rat |<ref name=":0" /> |- |GABA_A |10000+ |Rat |<ref name=":0" /> |- |GABA_B |10000+ |Rat |<ref name=":0" /> |- class="sortbottom" | colspan="4" |Values are K_i (nM). The smaller the value, the more strongly the drug binds to the site. |}

==Synthesis== thumb|center|500px|class=skin-invert-image|Synthesis:<ref>{{cite journal | vauthors = Craig PN, Gordon M, Lafferty JJ, Lester BM, Saggiomo AJ, Zirkle CL | title = Synthesis of Phenothiazines. VI. Certain 2-Substituted Phenothiazines and Their 10-Aminoalkyl Derivatives | journal = The Journal of Organic Chemistry | date = 1961 | volume = 26 | issue = 4 | pages = 1138–1143 | doi = 10.1021/jo01063a040 }}</ref> Patent:<ref>{{cite patent | country = US | number = 2877224 | inventor = Jacob RM, Georges RJ gdate = 1959 | assign1 = Rhone Poulenc Sa }}</ref> 2-Cyanophenothiazine [38642-74-9] ('''1''') 3-Chloro-2-methylpropyl(dimethyl)amine [23349-86-2] ('''2''')

== References == {{Reflist|30em}}

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