RT Journal Article SR Electronic T1 CARDIOVASCULAR PHARMACOLOGY OF TWO NEW β-ADRENERGIC RECEPTOR ANTAGONISTS JF Journal of Pharmacology and Experimental Therapeutics JO J Pharmacol Exp Ther FD American Society for Pharmacology and Experimental Therapeutics SP 174 OP 182 VO 149 IS 2 A1 H. C. Stanton A1 T. Kirchgessner A1 K. Parmenter YR 1965 UL http://jpet.aspetjournals.org/content/149/2/174.abstract AB The β-adrenergic receptor blocking activities of three agents, MJ 1999 [4-(2-isopropylamino-1-hydroxyethyl)methanesulfonanilide hydrochloride], MJ 1998 [4-(2-methylamino-1-hydroxypropyl) methanesulfonanilide hydrochloride] and pronethalol were compared using a number of cardiovascular procedures. The orders of β- receptor blocking potency based upon the capacity of the compounds to block the positive inotropic and/or chronotropic actions of isoproterenol on the heart were as follows: isolated perfused cat heart, MJ 1999 = pronethalol > MJ 1998; anesthetized dog (i. v.), MJ 1999 > pronethalol > MJ 1998. In addition, the three agents antagonized the positive inotropic actions on the heart elicited by electrical stimulation of the cardioaccelerator nerve, epinephrine and norepinephrine. Intrinsic cardiac stimulation was observed with low doses of pronethalol and with large doses of MJ 1998. No stimulating activities were observed with MJ 1999; a mild decrease in cardiac function, indicated by a slowed rate and decreased contractile force, occurred with larger doses. MJ 1999 did not alter arterial blood pressure, femoral arteriolar resistance, total peripheral resistance or coronary arteriolar resistance. All of these parameters were reduced by pronethalol. MJ 1998 acted as a vasoconstrictor in large doses and increased total peripheral resistance, arterial blood pressure and pulmonary arterial resistance when administered by intravenous infusion to the dog. MJ 1998 increased femoral arteriolar resistance but not coronary arteriolar resistance when administered intraarterially. MJ 1999, but not MJ 1998, partially protected guinea pigs from ouabain cardiotoxicity. In addition, MJ 1999 reduced the atrial rate of animals with atrial flutter induced by aconitine or injury stimulation. The order of decreasing cardiovascular toxicity based upon infusion studies in anesthetized dogs was: pronethalol > MJ 1999 > MJ 1998. The Williams & Wilkins Comapny