INHIBITION OF SYMPATHOMIMETIC EFFECTS ON THE CARDIOVASCULAR SYSTEM BY 4-(2-ISOPROPYLAMINO-1-HYDROXYETHYL)METHANESULFONANILIDE HYDROCHLORIDE (MJ 1999)

¹ Centro de Investigaciones Cardiológicas, University of Buenos Aires, Buenos Aires, Argentina

Several cardiovascular actions of 4-(2-isopropylamino-1-hydroxyethyl)methanesulfonanilide hydrochloride (MJ 1999) were studied. Isolated atria from guinea pigs were treated with 200 µg/ml of tyramine or obtained from reserpine-treated animals. In either situation, tissue exposure to 1 µg/ml of norepinephrine in the presence of MJ 1999 (10-5 M) failed to restore the response of the atrial pacemaker to tyramine or 1, 1-dimethyl-4-phenylpiperazinium iodide. Contrarily, restitution occurred when the tissues were exposed to norepinephrine alone. In addition, 0.5 µmol/kg i.a. of MJ 1999 significantly reduced the effects of sympathetic electrical stimulation and of tyramine in the perfused dog hind limb. The experiments indicate that MJ 1999 blocks the release of norepinephrine from the sympathetic nerve endings. Low doses (1-4 µmol/kg i.v.) of MJ 1999 showed little effect on the chronotropic responses to isoproterenol in chloralose-anesthetized, vagotomized dogs, whereas a sustained vasodilator blockade was observed. Under these experimental conditions, the pressor response to epinephrine was augmented but that to norepinephrine did not change significantly. Furthermore, inotropic and chronotropic effects induced by stellate ganglion stimulation were diminished (but not abolished) with 15 µmol/kg i.v. of MJ 1999. It is suggested that the dissociation between the cardiac and the vascular antagonism produced by this drug to the effects of isoproterenol indicates different intimacy of association with the respective receptors.