Inhibition of myocardial K+ channels by bromobenzoyl-methyladamantylamine, an adamantane derivative.
The effect of bromobenzoyl-methyladamantylamine (BMA) on transmembrane potentials and contractility of atrial and ventricular myocardium of guinea-pig and cat, as well as on transmembrane ionic currents of the frog atrial trabeculae was studied using conventional glass microelectrode and double sucrose-gap voltage clamp techniques. BMA markedly prolonged the action potential duration, depolarized the cell membrane, reduced the rate of rise of the action potential and exerted a positive inotropic effect on non-clamped myocardial preparations. The drug-induced pacemaker activity in ventricular working muscle of cat. Moreover, BMA antagonized the effects of the K+ channel activator acetylcholine in a dose-dependent manner. BMA was found to induce slow response action potentials in K+ -depolarized ventricular myocardium of guinea-pig. In voltage clamp experiments, BMA reduced the outward K+ current but had no effect on either rapid inward Na+ or slow inward Ca2+ currents. The results suggest that BMA is capable of selectively blocking the myocardial K+ channels.
D000109:Acetylcholine / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects; D000547:Amantadine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D005711:Gallopamil / Q000494:pharmacology; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects*; D066298:In Vitro Techniques; D007473:Ion Channels / Q000187:drug effects*; D008564:Membrane Potentials / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism; D011188:Potassium / Q000378:metabolism*; D011893:Rana esculenta
D007473:Ion Channels; D005711:Gallopamil; C036548:4-bromobenzoyl-methyladamantylamine; D000547:Amantadine; D000109:Acetylcholine; D011188:Potassium