Pirmenol inhibits muscarinic acetylcholine receptor-operated K+ current in the guinea pig heart.
We examined the effects of pirmenol and disopyramide on the muscarinic acetylcholine receptor-operated K+ current (I[K.ACh]) in atrial cells and on experimental atrial fibrillation in isolated guinea-pig hearts. In isolated atrial myocytes, both pirmenol and disopyramide concentration-dependently inhibited the I(K.ACh) induced by carbachol or intracellular loading of GTPgammaS. Their inhibitory effects on the carbachol-induced current were more potent than those on GTPgammaS-induced current, suggesting that these drugs inhibit I(K.ACh) mainly by blocking muscarinic receptors. In Langendorff-perfused hearts these drugs reversed the carbachol-induced decreases in effective refractory periods and atrial fibrillation threshold. These drugs may be useful for the prevention of vagally induced atrial fibrillation.
Watanabe
Y
Y
Department of Pharmacology, School of Medicine, Chiba University, Japan.
Hara
Y
Y
Tamagawa
M
M
Nakaya
H
H
D000200:Action Potentials; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D001281:Atrial Fibrillation / Q000188:drug therapy; D002217:Carbachol / Q000037:antagonists & inhibitors; D004206:Disopyramide / Q000494:pharmacology*; D004558:Electric Stimulation; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D018408:Patch-Clamp Techniques; D010880:Piperidines / Q000494:pharmacology*; D015221:Potassium Channels / Q000187:drug effects; D011976:Receptors, Muscarinic / Q000187:drug effects*
D000889:Anti-Arrhythmia Agents; D010880:Piperidines; D015221:Potassium Channels; D011976:Receptors, Muscarinic; D002217:Carbachol; D004206:Disopyramide; C024318:pirmenol