Cyamemazine

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]


Cyamemazine
Clinical data
Trade namesTercian
AHFS/Drugs.comInternational Drug Names
Routes of
administration		Oral, IM, IV
ATC code
Legal status
Legal status
  • In general: ℞ (Prescription only)
Pharmacokinetic data
Bioavailability10-70%
MetabolismHepatic
Elimination half-life10 hours
ExcretionUrine
Identifiers
IUPAC name
  • 10-(3-dimethylamino-2-methyl-propyl)phenothiazine-2-carbonitrile
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEMBL
ECHA InfoCard100.020.541
Chemical and physical data
FormulaC19H21N3S
Molar mass323.46 g·mol−1
3D model (JSmol)
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 Y
  • Key:SLFGIOIONGJGRT-UHFFFAOYSA-N Y
 NY (what is this?)  (verify)

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-HT2A, 5-HT2C, and 5-HT7.[9][10][11][12] These actions have been implicated in cyamemazine's anxiolytic effects (5-HT2C) and lack of extrapyramidal side effects (5-HT2A),[9][10] and despite being classified as a typical antipsychotic, it actually behaves like an atypical antipsychotic.[13]

Site Ki (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-HT1A 517 Human [14]
5-HT2A 1.5 Human [14]
5-HT2C 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]
GABAA >10,000 Rat [14]
GABAB >10,000 Rat [14]
Values are Ki (nM). The smaller the value,

the more strongly the drug binds to the site.

Synthsis
Synthesis:[15] Patent:[16]

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

References
  1. Index nominum, international drug ... - Google Books. 2000. ISBN 9783887630751.
  2. David J. Triggle (1996). Dictionary of Pharmacological Agents. Boca Raton: Chapman & Hall/CRC. p. 534. ISBN 0-412-46630-9.
  3. Sittig, Marshall (January 1988). Pharmaceutical manufacturing ... - Google Books. ISBN 9780815511441.
  4. Bret P, Bret MC, Queuille E (April 2009). "[Prescribing patterns of antipsychotics in 13 French psychiatric hospitals]". L'Encéphale (in French). 35 (2): 129–38. doi:10.1016/j.encep.2008.03.007. PMID 19393381. Archived from the original on 2013-02-13.
  5. "Stahl's Essential Psychopharmacology - Cambridge University Press".
  6. Bourin M, Nic Dhonnchadha BA, 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.
  7. Benyamina, Amine; Naassila, Mickaël; Bourin, Michel (2012-07-30). "Potential role of cortical 5-HT2A receptors in the anxiolytic action of cyamemazine in benzodiazepine withdrawal". Psychiatry Research. Elsevier BV. 198 (2): 307–312. doi:10.1016/j.psychres.2012.01.009. ISSN 0165-1781. PMID 22421069. S2CID 34830082.
  8. Bourin, Michel; Dailly, Eric; Hascöet, Martine (2006-06-07). "Preclinical and Clinical Pharmacology of Cyamemazine: Anxiolytic Effects and Prevention of Alcohol and Benzodiazepine Withdrawal Syndrome". CNS Drug Reviews. Wiley. 10 (3): 219–229. doi:10.1111/j.1527-3458.2004.tb00023.x. ISSN 1080-563X. PMC 6741725. PMID 15492772.
  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): 435–40. doi:10.1016/S0006-2952(02)01515-0. PMID 12527336.
  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): 412–7. doi:10.1007/s002130050010. PMID 10672635. S2CID 25162849. Archived from the original on 2002-01-12. Retrieved 2010-02-11.
  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): 235–9. doi:10.1016/S0014-2999(02)02489-5. PMID 12421652.
  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): 142–7. doi:10.1016/j.ejphar.2007.09.025. PMID 17936750.
  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): 134–9. doi:10.1007/s00210-002-0665-4. PMID 12595954. S2CID 682064.
  14. Hameg, Ahcène; Bayle, Franck; Nuss, Philippe; Dupuis, Philippe; Garay, Ricardo P.; Dib, Michel (2003-02-01). "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. ISSN 0006-2952. PMID 12527336.
  15. Craig, Paul N.; Gordon, Maxwell; Lafferty, John J.; Lester, Bruce M.; Saggiomo, Andrew J.; Zirkle, Charles L. (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. Jacob Robert Michel, Robert Jacques Georges, U.S. Patent 2,877,224 (1959 to Rhone Poulenc Sa).


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