Neuroleptic activity of 10-(4-methyl-1-piperazinyl)-thieno[3,2-b] [1,5]benzoxazepine and benzothiazepine derivatives.
Two series of compounds, structurally related to clozapine (CAS 5786-21-0), were tested for their neuroleptic activity. The derivatives 7-chloro-10-(4-methyl-1-piperazinyl)-thieno[3,2-b][1,5]benzoxazepine and 7-chloro-10-(4-methyl-1-piperazinyl)-thieno[3,2-b][1,5]benzothiazepine at high doses were not cataleptogenic and only very weakly antagonized the amphetamine-or apomorphine-induced stereotyped behaviour in the rat, whereas at low doses they antagonized the amphetamine-induced hypermotility in mice. Thus these compounds might be efficient neuroleptics with little propensity to cause extrapyramidal side effects. On the other hand, the unsubstituted compound 10-(4-methyl-1-piperazinyl)-thieno[3,2-b][1,5]benzothiazepine appeared to be an efficient neuroleptic agent with a greater propensity to cause these side effects.
Corral
C
C
Instituto de Química Médica (CSIC), Madrid, Spain.
Lissavetzky
J
J
Valdeolmillos
A
A
Bravo
L
L
Darias
V
V
Sánchez Mateo
C
C
D000818:Animals; D014150:Antipsychotic Agents / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D001831:Body Temperature / Q000187:drug effects; D002375:Catalepsy / Q000139:chemically induced; D003913:Dextroamphetamine / Q000494:pharmacology; D015259:Dopamine Agents / Q000494:pharmacology; D005106:Exploratory Behavior / Q000187:drug effects; D007928:Lethal Dose 50; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D009125:Muscle Relaxants, Central / Q000138:chemical synthesis / Q000494:pharmacology; D010077:Oxazepines / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D010879:Piperazines / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D013239:Stereotyped Behavior / Q000187:drug effects; D013841:Thiazepines / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity
D014150:Antipsychotic Agents; D015259:Dopamine Agents; D009125:Muscle Relaxants, Central; D010077:Oxazepines; D010879:Piperazines; D013841:Thiazepines; D003913:Dextroamphetamine