Cyamemazine

Cyamemazine
Clinical data
Trade names	Tercian
AHFS/Drugs.com	International Drug Names
Routes of; administration	Oral, IM, IV
ATC code	N05AA06 (WHO) ;
Legal status
Legal status	In general: ℞ (Prescription only);
Pharmacokinetic data
Bioavailability	10-70%
Metabolism	Hepatic
Elimination half-life	10 hours
Excretion	Urine
Identifiers
	IUPAC name 10-(3-dimethylamino-2-methyl-propyl)phenothiazine-2-carbonitrile;
CAS Number	3546-03-0 ;
PubChem CID	62865;
IUPHAR/BPS	84;
DrugBank	DB09000 ;
ChemSpider	56597 ;
UNII	A2JGV5CNU4;
KEGG	D07307 ;
ChEMBL	ChEMBL2104153 ;
CompTox Dashboard (EPA)	DTXSID80863190 ;
ECHA InfoCard	100.020.541
Chemical and physical data
Formula	C19H21N3S
Molar mass	323.46 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES N#Cc2cc1N(c3c(Sc1cc2)cccc3)CC(C)CN(C)C;
	InChI InChI=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 ; Key:SLFGIOIONGJGRT-UHFFFAOYSA-N ;
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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.^[1]^[2]^[3]^[4]

Medical use

It is used for the treatment of schizophrenia and, especially, for psychosis-associated anxiety, due to its unique anxiolytic efficacy.^[5]^[6]

It is also used to reduce anxiety associated with benzodiazepine withdrawal syndrome and anxiety in depression with suicidal tendency.^[7]

Side effects

Here are some of the most common side effects and related incidence:^[8]

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,^[9] it additionally produces potent blockade of several serotonin receptors, including 5-HT_2A, 5-HT_2C, and 5-HT₇.^[9]^[10]^[11]^[12] These actions have been implicated in cyamemazine's anxiolytic effects (5-HT_2C) and lack of extrapyramidal side effects (5-HT_2A),^[9]^[10] and despite being classified as a typical antipsychotic, it actually behaves like an atypical antipsychotic.^[13]

Site	K_i (nM)	Species	Ref
H₁	9.3	Guinea pig	^[14]
H₂	351	Guinea pig	^[14]
H₃	>10,000	Rat	^[14]
M₁	13	Human	^[14]
M₂	42	Human	^[14]
M₃	32	Human	^[14]
M₄	12	Human	^[14]
M₅	35	Human	^[14]
5-HT_1A	517	Human	^[14]
5-HT_2A	1.5	Human	^[14]
5-HT_2C	12	Human	^[14]
5-HT₃	2,943	Human	^[14]
5-HT₇	22	Human	^[14]
D₁	3.8	Human	^[14]
D₂	5.8	Human	^[14]
D₃	2.5	Human	^[14]
D₄	5.3	Human	^[14]
α₁	2.3	Rat	^[14]
α₂	1320	Rat	^[14]
GABA_A	>10,000	Rat	^[14]
GABA_B	>10,000	Rat	^[14]
Values are K_i (nM). The smaller the value, the more strongly the drug binds to the site.

Synthesis

Synthesis:^[15] Patent:^[16]

2-Cyanophenothiazine [38642-74-9] (1) 3-Chloro-2-methylpropyl(dimethyl)amine [23349-86-2] (2)

References

^ Index Nominum, International Drug. Taylor & Francis. 2000. ISBN 978-3-88763-075-1.
^ Triggle DJ (1996). Dictionary of Pharmacological Agents. Boca Raton: Chapman & Hall/CRC. p. 534. ISBN 0-412-46630-9.
^ Sittig M (January 1988). Pharmaceutical manufacturing ... - Google Books. Noyes Publications. ISBN 9780815511441.
^ Bret P, Bret MC, Queuille E (April 2009). "[Prescribing patterns of antipsychotics in 13 French psychiatric hospitals]". L'Encephale (in French). 35 (2): 129–138. doi:10.1016/j.encep.2008.03.007. PMID 19393381. Archived from the original on 2013-02-13.
^ "Cyamemazine". Stahl's Essential Psychopharmacology. Cambridge University Press.
^ Bourin M, Claude Colombel M, Dib M, Hascoët M (September 2001). "Cyamemazine as an anxiolytic drug on the elevated plus maze and light/dark paradigm in mice". Behavioural Brain Research. 124 (1): 87–95. doi:10.1016/S0166-4328(01)00238-8. PMID 11423169. S2CID 43312295.
^ Benyamina A, Naassila M, Bourin M (July 2012). "Potential role of cortical 5-HT(2A) receptors in the anxiolytic action of cyamemazine in benzodiazepine withdrawal". Psychiatry Research. 198 (2). Elsevier BV: 307–312. doi:10.1016/j.psychres.2012.01.009. PMID 22421069. S2CID 34830082.
^ Bourin M, Dailly E, Hascöet M (2006-06-07). "Preclinical and clinical pharmacology of cyamemazine: anxiolytic effects and prevention of alcohol and benzodiazepine withdrawal syndrome". CNS Drug Reviews. 10 (3). Wiley: 219–229. doi:10.1111/j.1527-3458.2004.tb00023.x. PMC 6741725. PMID 15492772.
^ ^a ^b ^c Hameg A, Bayle F, Nuss P, Dupuis P, Garay RP, Dib M (February 2003). "Affinity of cyamemazine, an anxiolytic antipsychotic drug, for human recombinant dopamine vs. serotonin receptor subtypes". Biochemical Pharmacology. 65 (3): 435–440. doi:10.1016/S0006-2952(02)01515-0. PMID 12527336.
^ ^a ^b Alvarez-Guerra M, d'Alché-Birée F, Wolf WA, Vargas F, Dib M, Garay RP (January 2000). "5-HT3- and 5-HT2C-antagonist properties of cyamemazine: significance for its clinical anxiolytic activity". Psychopharmacology. 147 (4): 412–417. doi:10.1007/s002130050010. PMID 10672635. S2CID 25162849. Archived from the original on 2002-01-12. Retrieved 2010-02-11.
^ Alvarez-Guerra M, Hameg A, Bayle F, Dib M, Garay RP (November 2002). "5-HT2A receptor antagonist properties of cyamemazine in rat and guinea pig smooth muscle". European Journal of Pharmacology. 454 (2–3): 235–239. doi:10.1016/S0014-2999(02)02489-5. PMID 12421652.
^ Benyamina A, Arbus C, Nuss P, Garay RP, Neliat G, Hameg A (January 2008). "Affinity of cyamemazine metabolites for serotonin, histamine and dopamine receptor subtypes". European Journal of Pharmacology. 578 (2–3): 142–147. doi:10.1016/j.ejphar.2007.09.025. PMID 17936750.
^ Peinado J, Hameg A, Garay RP, Bayle F, Nuss P, Dib M (February 2003). "Reduction of extracellular dopamine and metabolite concentrations in rat striatum by low doses of acute cyamemazine". Naunyn-Schmiedeberg's Archives of Pharmacology. 367 (2): 134–139. doi:10.1007/s00210-002-0665-4. PMID 12595954. S2CID 682064.
^ ^a ^b ^c ^d ^e ^f ^g ^h ⁱ ^j ^k ^l ^m ⁿ ^o ^p ^q ^r ^s ^t ^u Hameg A, Bayle F, Nuss P, Dupuis P, Garay RP, Dib M (February 2003). "Affinity of cyamemazine, an anxiolytic antipsychotic drug, for human recombinant dopamine vs. serotonin receptor subtypes". Biochemical Pharmacology. 65 (3): 435–440. doi:10.1016/s0006-2952(02)01515-0. PMID 12527336.
^ Craig PN, Gordon M, Lafferty JJ, Lester BM, Saggiomo AJ, Zirkle CL (1961). "Synthesis of Phenothiazines. VI. Certain 2-Substituted Phenothiazines and Their 10-Aminoalkyl Derivatives". The Journal of Organic Chemistry. 26 (4): 1138–1143. doi:10.1021/jo01063a040.
^ US 2877224, Jacob RM, Georges RJ gdate = 1959, assigned to Rhone Poulenc Sa

[urlIndex_nominum,_international_drug_..._-_Google_Books-1] Index Nominum, International Drug. Taylor & Francis. 2000. ISBN 978-3-88763-075-1.

[isbn0-412-46630-9-2] Triggle DJ (1996). Dictionary of Pharmacological Agents. Boca Raton: Chapman & Hall/CRC. p. 534. ISBN 0-412-46630-9.

[urlPharmaceutical_manufacturing_..._-_Google_Books-3] Sittig M (January 1988). Pharmaceutical manufacturing ... - Google Books. Noyes Publications. ISBN 9780815511441.

[pmid19393381-4] Bret P, Bret MC, Queuille E (April 2009). "[Prescribing patterns of antipsychotics in 13 French psychiatric hospitals]". L'Encephale (in French). 35 (2): 129–138. doi:10.1016/j.encep.2008.03.007. PMID 19393381. Archived from the original on 2013-02-13.

[urlStahls_Essential_Psychopharmacology_-_Cambridge_University_Press-5] "Cyamemazine". Stahl's Essential Psychopharmacology. Cambridge University Press.

[pmid11423169-6] Bourin M, Claude Colombel M, Dib M, Hascoët M (September 2001). "Cyamemazine as an anxiolytic drug on the elevated plus maze and light/dark paradigm in mice". Behavioural Brain Research. 124 (1): 87–95. doi:10.1016/S0166-4328(01)00238-8. PMID 11423169. S2CID 43312295.

[Benyamina_Naassila_Bourin_2012_pp._307–312-7] Benyamina A, Naassila M, Bourin M (July 2012). "Potential role of cortical 5-HT(2A) receptors in the anxiolytic action of cyamemazine in benzodiazepine withdrawal". Psychiatry Research. 198 (2). Elsevier BV: 307–312. doi:10.1016/j.psychres.2012.01.009. PMID 22421069. S2CID 34830082.

[Bourin_Dailly_Hascöet_pp._219–229-8] Bourin M, Dailly E, Hascöet M (2006-06-07). "Preclinical and clinical pharmacology of cyamemazine: anxiolytic effects and prevention of alcohol and benzodiazepine withdrawal syndrome". CNS Drug Reviews. 10 (3). Wiley: 219–229. doi:10.1111/j.1527-3458.2004.tb00023.x. PMC 6741725. PMID 15492772.

[pmid12527336-9] Hameg A, Bayle F, Nuss P, Dupuis P, Garay RP, Dib M (February 2003). "Affinity of cyamemazine, an anxiolytic antipsychotic drug, for human recombinant dopamine vs. serotonin receptor subtypes". Biochemical Pharmacology. 65 (3): 435–440. doi:10.1016/S0006-2952(02)01515-0. PMID 12527336.

[pmid10672635-10] Alvarez-Guerra M, d'Alché-Birée F, Wolf WA, Vargas F, Dib M, Garay RP (January 2000). "5-HT3- and 5-HT2C-antagonist properties of cyamemazine: significance for its clinical anxiolytic activity". Psychopharmacology. 147 (4): 412–417. doi:10.1007/s002130050010. PMID 10672635. S2CID 25162849. Archived from the original on 2002-01-12. Retrieved 2010-02-11.

[pmid12421652-11] Alvarez-Guerra M, Hameg A, Bayle F, Dib M, Garay RP (November 2002). "5-HT2A receptor antagonist properties of cyamemazine in rat and guinea pig smooth muscle". European Journal of Pharmacology. 454 (2–3): 235–239. doi:10.1016/S0014-2999(02)02489-5. PMID 12421652.

[pmid17936750-12] Benyamina A, Arbus C, Nuss P, Garay RP, Neliat G, Hameg A (January 2008). "Affinity of cyamemazine metabolites for serotonin, histamine and dopamine receptor subtypes". European Journal of Pharmacology. 578 (2–3): 142–147. doi:10.1016/j.ejphar.2007.09.025. PMID 17936750.

[pmid12595954-13] Peinado J, Hameg A, Garay RP, Bayle F, Nuss P, Dib M (February 2003). "Reduction of extracellular dopamine and metabolite concentrations in rat striatum by low doses of acute cyamemazine". Naunyn-Schmiedeberg's Archives of Pharmacology. 367 (2): 134–139. doi:10.1007/s00210-002-0665-4. PMID 12595954. S2CID 682064.

[:0-14] ^ ^a ^b ^c ^d ^e ^f ^g ^h ⁱ ^j ^k ^l ^m ⁿ ^o ^p ^q ^r ^s ^t ^u Hameg A, Bayle F, Nuss P, Dupuis P, Garay RP, Dib M (February 2003). "Affinity of cyamemazine, an anxiolytic antipsychotic drug, for human recombinant dopamine vs. serotonin receptor subtypes". Biochemical Pharmacology. 65 (3): 435–440. doi:10.1016/s0006-2952(02)01515-0. PMID 12527336.

[15] Craig PN, Gordon M, Lafferty JJ, Lester BM, Saggiomo AJ, Zirkle CL (1961). "Synthesis of Phenothiazines. VI. Certain 2-Substituted Phenothiazines and Their 10-Aminoalkyl Derivatives". The Journal of Organic Chemistry. 26 (4): 1138–1143. doi:10.1021/jo01063a040.

[16] US 2877224, Jacob RM, Georges RJ gdate = 1959, assigned to Rhone Poulenc Sa

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