Antihypertensive activity of a new ACE-inhibitor, SCH 33844, during repeated administration in spontaneously hypertensive rats.
The antihypertensive activity of SCH 33844, a new angiotensin converting enzyme inhibitor, was investigated in conscious spontaneously hypertensive rats during a 3-week treatment regimen and for 1 week following drug withdrawal. SCH 33844 was given once daily at 2 dose levels (1 and 5 mg/kg orally) and its effects were compared with those of captopril (60 mg/kg orally). Systolic blood pressure was recorded twice weekly just before administration and at varying time intervals up to 6 hr after dosing; recordings were continued for 1 week after drug withdrawal. SCH 33844 was found to produce dose-related antihypertensive effects. Given at 1 mg/kg, the compound elicited small but significant blood pressure changes during the treatment. After drug withdrawal, systolic blood pressure returned to pre-drug levels within 1 week. SCH 33844 at 5 mg/kg, and captopril at 60 mg/kg, both reduced blood pressure markedly and to a similar extent. After each administration the effect was rapid in onset, lasted for over 6 hr and was not subject to tolerance. Drug withdrawal resulted in a gradual return of systolic blood pressure toward pre-treatment levels within 1 week, with no evidence of rebound phenomena. These results indicate that SCH 33844, like captopril, produces an effective antihypertensive action throughout a repeated dosing.
D000806:Angiotensin-Converting Enzyme Inhibitors; D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D002216:Captopril / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004656:Enalapril / Q000031:analogs & derivatives* / Q000627:therapeutic use; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR; D013375:Substance Withdrawal Syndrome / Q000503:physiopathology
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D004656:Enalapril; C052555:spirapril; D002216:Captopril