Synthesis and pharmacological evaluation of some phenothiazines as antidepressants.
10-Hydrazino acetyl phenothiazine (II) has been converted to N-10-acetyl amino phenothiazine-N-phenyl thiourea (III) which have been converted to 3-aryl-1-(10-phenothiazine acetyl amino)-2,3-dihydro-2-thioxo-4,6-(1H,5H) pyrimidinones (IV) on condensation with aryl amines and aryl aldehydes yielded 3-aryl-1-(10-Phenothiazine acetyl amino)-5-(substituted phenyl amino methyl)-2,3-dihydro-2-thioxo-4,6-(1H, 5H) pyrimidinediones (Va-k) and 3-aryl-1-(10-phenothiazine acetyl amino)-5-(substituted phenylidine)-2,3-dihydro-2-thioxo-4,6-(1H, 5H) pyrimidinediones (vl-o). The compounds were screened for their antidepressant activity against a tricyclic antidepressant (imipramine). Compounds Va, Vf, Vm and Vi exhibited activity better than imipramine with no toxicity (ALD50 greater than 1000 mg/kg) but Vi showed some side effects.
Singh
V
V
Department of Pharmacology and Therapeutics, King George's Medical College, Lucknow, India.
Khanna
R
R
Srivastava
V K
VK
Palit
G
G
Shanker
K
K
D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D000928:Antidepressive Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D003863:Depression / Q000188:drug therapy; D004357:Drug Synergism; D005260:Female; D008297:Male; D051379:Mice; D009422:Nervous System Diseases / Q000139:chemically induced / Q000503:physiopathology; D010640:Phenothiazines / Q000138:chemical synthesis* / Q000494:pharmacology; D010862:Pilocarpine / Q000494:pharmacology; D012110:Reserpine / Q000037:antagonists & inhibitors; D012472:Salivation / Q000187:drug effects
D000928:Antidepressive Agents; D010640:Phenothiazines; D010862:Pilocarpine; D012110:Reserpine; D000661:Amphetamine