Antihypertensive and cardiac effects of two novel beta-adrenoceptor blocking drugs.
Two new beta-adrenoceptor blocking drugs with acute antihypertensive and positive inotropic effects are described: Compound A (2-[4-(3-tert.butylamino-2-hydroxypropoxy)phenyl]-4-trifluoromethylimidazole) and MK-761 (2-(3-tert.butylamine-2-hydroxypropoxy)-3-cyanopyridine hydrochloride). In SH rats both compounds, given orally, lowered arterial pressure and were more potent than hydralazine. The antihypertensive effect of compound A but not of MK-761 was antagonized by timolol. Both compounds had positive inotropic activity on cat heart papillary muscles; these effects were antagonized by timolol. The pretreatment of animals with reserpine greatly reduced the positive inotropic effect of MK-761 but not of compound A. The acute antihypertensive and positive inotropic effects of compound A are like to be at least partially due to stimulation of beta-adrenoceptors, e.g. intrinsic sympathomimetic activity. The effects of MK-761 on the same parameters appear to be mediated by different mechanisms.
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents; D001794:Blood Pressure / Q000187:drug effects*; D002082:Butylamines / Q000494:pharmacology*; D006321:Heart / Q000503:physiopathology*; D006339:Heart Rate / Q000187:drug effects; D006830:Hydralazine / Q000494:pharmacology; D006973:Hypertension / Q000235:genetics / Q000503:physiopathology; D007093:Imidazoles / Q000494:pharmacology*; D009200:Myocardial Contraction / Q000187:drug effects*; D011725:Pyridines / Q000494:pharmacology*; D051381:Rats
D000319:Adrenergic beta-Antagonists; D000959:Antihypertensive Agents; D002082:Butylamines; D007093:Imidazoles; D011725:Pyridines; D006830:Hydralazine; C021276:MK 761