Mechanism of the Positive Inotropic Actions of Quaternary Ammonium Compounds

ABSTRACT

The mechanism of the positive inotropic responses to quaternary ammonium compounds (tetraethylam-monium, tetra-n-propylammouium, trimethylethylamm-onium trimethyl-n-butylammonium, trimethyl-n-penty-lammonium, trimethyl-n-hexylammonium, trimethyI-phenylammonium, trimethylbenzylammonium, triethyl-phenylammonium and m-hydroxyphenyltrimethylam-monium) was examined on the atropinized papillarymuscle of cats. After pretreatment with dichloro-isoproterenol, all the quaternary ammonium compounds failed to produce their usual positive inotropic activities. Bretylium or TM-10, which specifically interferes with the release and/or synthesis of adrenergic mediators, rendered papillary muscle unresponsive to quaternary ammonium compounds but responsive to norepinephrine. Quaternary ammonium compounds also failed to produce their positive inotropic activity on papillary muscle whose catecholamines were a1most completely dep1eted by treatment with reserpine. Surgical removal of the sympathetic innervation to the heart resulted in a marked reduction of myocardial catecholamines. The positive inotropic responses to quaternary ammonium compounds were markedly suppressed in papillary muscle obtained from bilaterally-sympathectomized cats with degenerated postganglionic sympathetic nerve fibers to the heart. From the above results, it appears that quaternary ammonium compounds act at a common site to effect positive inotropic activities which are mediated via a catecholamine-release mechanism.