IN-VIVO PHARMACOLOGY OF SC-51316, A NONPEPTIDIC ANGIOTENSIN-II RECEPTOR ANTAGONIST

The depressor activity of a novel nonpeptidic angiotensin II (AII) rec eptor antagonist, SC-51316 bi-phenyl]-4'-yl]-methyl]-3H-1,2,4-triazol- 3-one), is described. In anesthetized, ganglion-blocked rats, intraven ous administration of SC-51316 inhibited the pressor response to an in fusion of All. To determine antihypertensive efficacy, conscious, spon taneously hypertensive rats were administered SC-51316 (30 mg/kg intra gastrically) daily for 5 days. Blood pressure was reduced in a similar manner to that observed with the angiotensin converting enzyme inhibi tor enalapril (10 mg/ kg intragastrically). SC-51316 had no effect on heart rate. In conscious, sodium-deficient dogs, administration of SC- 51316 (30 mg/kg orally) or enalapril (10 mg/kg orally) lowered blood p ressure similarly over a 24 h observation period. Thus, SC-51316 antag onizes the activity of All in vivo and is an orally active, antihypert ensive agent.