Inhibition of sympathetic nervous system by mexiletine, an antiarrhythmic agent, and its antagonism against ouabain.
The effects of mexiletine on the sympathetic nervous system and the antiarrhythmic action were studied and compared with those of lidocaine. In isolated blood vessels, mexiletine inhibited the contractile responses to nicotine, tyramine and electrical transmural stimulation, but did not affect the contractile responses to exogenous norepinephrine and KCl. Lidocaine also inhibited the contractile responses to nicotine and electrical transmural stimulation, but such an inhibitory activity was weaker than that of mexiletine. Lidocaine did not affect the contraction induced by tyramine and enhanced significantly contractile responses to exogenous norepinephrine and KCl. Mexiletine and lidocaine inhibited the release of 3H-norepinephrine from the isolated rabbit pulmonary artery induced by transmural electrical stimulation. Mexiletine increased the dose of ouabain required for the occurrence of arrhythmia and cardiac arrest. These effects of mexiletine did not occur after reserpine. Though lidocaine increased the dose of ouabain required for cardiac arrest, the development of arrhythmia was not prevented. The increase in the dose of ouabain required for cardiac arrest induced by lidocaine was not affected by reserpine. On the other hand, mexiletine and lidocaine prevented the epinephrine-induced arrhythmia. These results suggested that the antagonism of mexiletine against ouabain may be due not only to the previously reported quinidine-like direct action on the myocardium, but also partially to the inhibitory action on releasing norepinephrine from the sympathetic nerve terminals.
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D001145:Arrhythmias, Cardiac / Q000139:chemically induced / Q000503:physiopathology; D004558:Electric Stimulation; D004837:Epinephrine / Q000037:antagonists & inhibitors / Q000378:metabolism; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008012:Lidocaine / Q000494:pharmacology; D008297:Male; D008801:Mexiletine / Q000494:pharmacology*; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009538:Nicotine / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism / Q000494:pharmacology; D010042:Ouabain / Q000037:antagonists & inhibitors*; D011169:Portal Vein / Q000187:drug effects; D011189:Potassium Chloride / Q000494:pharmacology; D011437:Propylamines / Q000494:pharmacology*; D011651:Pulmonary Artery / Q000187:drug effects; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D013565:Sympatholytics; D014439:Tyramine / Q000494:pharmacology
D011437:Propylamines; D013565:Sympatholytics; D008801:Mexiletine; D010042:Ouabain; D011189:Potassium Chloride; D009538:Nicotine; D008012:Lidocaine; D009638:Norepinephrine; D014439:Tyramine; D004837:Epinephrine