EFFECT OF 4,4'-BIPHENYLENEBIS-[(2-OXOETHYLENE)-BIS-(2,2-DIETHOXYETHYL)]DIMETHYLAMMONIUM DIBROMIDE (DMAE) ON ACCUMULATION AND NICOTINE-INDUCED RELEASE OF NOREPINEPHRINE IN THE HEART

¹ Department of Pharmacology, University of Virginia School of Medicine, Charlottesville, Virginia

4,4'-Biphenylenebis-[(2-oxoethylene)-bis-(2,2-diethoxyethyl)]dimethylammonium dibromide (DMAE) produces a dose-related inhibition of norepinephnine accumulation in both isolated rat atria and the perfused guinea-pig heart with the maximum inhibition observed with 0.75 to 1.5 x 10^-5 M DMAE in time atria and 4.5 x 10^-5 M in the perfused heart. Similarly, DMAE antagonizes the release of l-³H-norepinephrine produced by tyramine and potentiates the chronotropic effect of l-nonepinephnine. These data are consistent with the view that DMAE produces potentiation of the effects of norepinephrine by inhibiting neuronal uptake in a cocaine-like fashion. DMAE also blocks the positive chronotropic effect of two nicotinic agonists, namely, nicotine and 1, 1-dimethyl-4-phenylpiperazinium iodide,and prevents the nicotine-induced release of ³H-norepinephrine from adrenergic nerve terminals. The nicotinic receptor appears more sensitive to DMAE than the receptor responsible for transporting norepinephrine across the neuronal membrane.