Derivatives of tetrahydro-1,4-benzodiazepines as potential antihypertensive agents.
4-Amidino derivatives and quaternary salts of tetrahydro-1,4-benzodiazepines were synthesized and evaluated for antihypertensive activity in conscious rats by the oral route. Included in this study were derivatives of 1,2,4,5,6,7-hexahydropyrrolo[3,2,1-jk][1,4]benzodiazepine and 1,2,3,4,8,9,10,11-octahydro[1,4]diazepino[6,5,4-jk]carbazole in which the 1 and 9 positions of tetrahydro-1,4-benzodiazepine are linked by an ethylene and a cyclohexenyl chain, respectively. Four compounds exhibited marked blood pressure lowering activity (greater than 50 mmHg) at doses of 75 mg/kg. Further study indicated that these compounds are effective by impairing transmission in the sympathetic nervous system.
D000818:Animals; D000959:Antihypertensive Agents / Q000138:chemical synthesis*; D001569:Benzodiazepines / Q000138:chemical synthesis* / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D004558:Electric Stimulation; D005260:Female; D006973:Hypertension / Q000503:physiopathology; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000502:physiology
D000959:Antihypertensive Agents; D001569:Benzodiazepines; D010656:Phenylephrine