THE SYMPATHOMIMETIC EFFECT OF GALLAMINE ON THE HEART

¹ Division of Clinical Pharmacology, Department of Pharmacology, The University of Texas Southwestern Medical School at Dallas, Dallas Texas

The quaternary ammonium neuromuscular blocking drug, gallamine, was found to increase the rate and contractile force of guinea-pig and cat atria in vitro; cardiac rate and right ventricular contractile force were also increased in vivo in the anesthetized open-chest cat. Positive inotropic responses to gallamine were inhibited in vitro by propranolol, 2 x 10^-6 M, and in vivo by prior administration of propranolol, 0.5 mg/kg i.v. Atria taken from guinea pigs treated with reserpine, 2.5 mg/kg i.p. 24 hours previously, failed to respond to gallamine or responded only poorly. The positive inotropic response to gallamine in guinea-pig atria in vitro was not inhibited by atropine, 1 x 10^-7 M; d-tubocurarine, 1 x 10^-4 M; hexamethonium, 1 x 10^-5 M; or cocaine, 2.9 x 10^-5 M. Tachyphylaxis to this response developed rapidly in vitro and could be reversed by exposure of the tissue to l-norepinephrine, 1 x 10^-7 M, for 10 minutes. Cross-tachyphylaxis did not occur between gallamine and tyramine. Gallamine, 5 x 10^-4 M, did not inhibit the uptake of l-H³norepinephrine by guinea-pig atria in vitro. The atropinelike action of gallamine on the heart was confirmed and pA₂ values for the acetylcholinegallamine interaction were estimated in isolated atria and in ileal segments taken from guinea pigs. It is concluded that gallarnine releases norepinephrine from adrenergic nerve endings in the heart by an unidentified mechanism which is not identical with that of either tyrarnine, nicotine or bretylium.