Pharmacological Properties of AR-C239, 2-[2-[4 (O-Methoxyphenyl)-Piperazine-1-Y1]-Ethyl]4,4-Dimethyl-1, 3(2H-4H) Isoquinolinedione, A New α-Adrenoceptor Blocking Drug

Abstract

Summary In pentobarbital-treated dogs and rats. AR-C239, a new and potent α-adrenoceptor blocking drug, competitively antagonized pressor responses to adrenaline and inhibited pressor responses to noradrenaline, phenylephrine, tyramine, and dimethylphenylpiperazinium. Injected intravenously into closed-chest dogs, AR-C239 (3 - 50 $mUg/kg) induced a progressive fall in blood pressure, heart rate, and sympathetic nerve activity. The drug appears to be devoid of direct vasodilator action, and the fall in blood pressure results from the peripheral α-blockade. AR-C239 did not change the tachycardia induced by stimulation of the cardiac nerve in dogs and, at least in this preparation, seems to be a specific α1-adrenoceptor blocking drug. When administered into the cisterna magna of dogs, AR-C239 did not have any centrally mediated cardiovascular actions and failed to block the inhibitory effects of clonidine on blood pressure and heart rate. AR-C239 did not modify the functioning of the baroreflex arc. Due to its specificity for α1-adrenoceptors, AR-C239 may be useful for characterizing α-adrenoceptors.