title: Effect of mono- and diaminopyridines on release of [3H]norepinephrine from isolated guinea-pig atrium.
abstract: Neurochemical evidence has been obtained that 4-aminopyridine, 3,4-diaminopyridine and 3,3-dimethyl-1-(4-amino-3-pyridyl)urea HBr (LF-14), concentration-dependently enhanced the stimulation-evoked release of [3H]norepinephrine ([3H]NE) from isolated guinea-pig atrium. The effects of aminopyridines, compounds known to inhibit potassium channels, were Ca0-dependent. High pressure liquid chromatography, combined with radiochemical detection, indicated that the increased stimulated release of radioactivity was due to [3H]NE. Since the aminopyridines studied also enhanced the release of [3H]NE from atrium treated with cocaine, a blocker of uptake1, it seems likely that the increased release of NE caused by the aminopyridines is due to the enhanced release of NE from sympathetic axon terminals and not to the inhibition of reuptake. It is probable that the sympathomimetic cardiac effects (positive inotropic and chronotropic effect) of aminopyridines observed in animal experiments is due to the increased release of NE, caused by these compounds.
mesh_terms: D015761:4-Aminopyridine / Q000031:analogs & derivatives; D000077770:Amifampridine; D000631:Aminopyridines / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000502:physiology; D003042:Cocaine / Q000494:pharmacology; D004558:Electric Stimulation; D005260:Female; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects*; D066298:In Vitro Techniques; D008297:Male; D009206:Myocardium / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism*
chemical_list: D000631:Aminopyridines; C040030:LF 14; D015761:4-Aminopyridine; D003042:Cocaine; D000077770:Amifampridine; D002118:Calcium; D009638:Norepinephrine