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 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 Y
PubChem CID	62865
IUPHAR/BPS	84
DrugBank	DB09000 N
ChemSpider	56597 Y
UNII	A2JGV5CNU4
KEGG	D07307 Y
ChEMBL	ChEMBL2104153 N
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 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-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	Ki (nM)	Species	Ref
H1	9.3	Guinea pig	[14]
H2	351	Guinea pig	[14]
H3	10000+	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	2943	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	10000+	Rat	[14]
GABAB	10000+	Rat	[14]
Values are Ki (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)