Antihypertensive effect of AJ-2615, a novel calcium entry blocker, in experimental hypertensive rats and dogs

AJ-2615, 11-[4-{4-(4-fluorophenyl)-1-piperazinyl} butyrylamino]-6, 11-dihydrodibenzo [b, e] thiepine maleate, is a novel calcium entry blocker with α1 -adrenoceptor blocking activity. Antihypertensive activity of AJ-2615 was investigated in experimental hyper-tensive rats and dogs and compared with those of calcium entry blockers (diltiazem, nifedipine and nicardipine). On single oral administration to SHR, renal and DOCA-salt hypertensive rats (10-100 mg/kg) and renal hypertensive dogs (2.5-10.0 mg/kg), AJ-2615 produced a dose-related antihypertensive effect. The hypotensive effect of AJ-2615 appeared gradually and reached a maximum at 5-9 hr, while the maximum effect of the other three calcium blockers was observed within an hour after dosing. The hypotensive effect of AJ-2615 persisted for over 20 hr, but those of the reference compounds lasted for less than 5 hr. During repeated oral administration to SHR (10-50 mg/kg, once daily for 1 week) and renal hypertensive dogs (10 mg/kg, once daily for 4 weeks), AJ-2615 reduced the daily starting blood pressure and did not induced any tolerance. Besides these antihypertensive characteristics. AJ-2615 exhibited a protective effect against ischemic changes of the myocardium in experimental models.