PHARMACOLOGICAL PROFILE OF ME3221, A NOVEL ANGIOTENSIN-II RECEPTOR ANTAGONIST

The pharmacological profile of a new surmountable angiotensin AT(1) re ceptor antagonist, ME3221, imethyl-4-[[2'-(1H-tetrazol-5-yl)-1,1'-biph enyl-4- yl]methoxy]pyridine, was studied in several animal models, and was compared with that of losartan. EF2831, etrazol-5-yl)-1,1'-biphen yl-4-yl]methoxy]pyridine, a metabolite of ME3221, is also a surmountab le angiotensin AT(1) receptor antagonist, whose potency was 1/30 that of ME3221 in vitro, but equal to or 1/3 of that of ME3221 in in vivo e xperiments. In rats and marmosets, ME3221 antagonized angiotensin II-i nduced presser responses, but did not affect bradykinin-induced depres sor responses. ME3221 lowered the blood pressure in renal hypertensive rats and spontaneously hypertensive rats (SHR), and its ED(25) value was 3 times that of losartan. Repeated administration of ME3221 to SHR had a stable and long-lasting antihypertensive effect without influen cing heart rate. Thus ME3221, like losartan, may be useful in the trea tment of renal and essential hypertension.