Mirro M J, Webel R R, Kelly K J, Grina L A
J Cardiovasc Pharmacol. 1981 Nov-Dec;3(6):1312-20. doi: 10.1097/00005344-198111000-00019.
The antifibrillatory property of bretylium tosylate was first observed in experimental atrial fibrillation, yet the cellular basis for this phenomenon has not been explored. The purpose of this study was to determine the electrophysiologic properties of bretylium tosylate on guinea pig atrial myocardium in the presence and absence of cholinergic influence. Bretylium (10(-6) M - 10(-4) M) produced a concentration-dependent prolongation of atrial action potential duration with a threshold concentration of 10(-5) M. This direct effect of bretylium was unaltered by blockade of beta-adrenergic receptors with propranolol (10(-6) M) or blockade of alpha-adrenergic receptors with phentolamine (10(-6) M). In a second series of experiments the muscarinic receptor blocking properties of bretylium were determined. Acetylcholine produced a concentration-dependent shortening of action potential duration in paced (200 ms) left atrial muscle strips. This well-recognized muscarinic effect was unaltered in the presence of bretylium (10(-6) M - 10(-3) M). These data indicate that bretylium tosylate physiologically exerts direct effects on the atrial myocardium to prolong action potential duration. This compound does not appear to physiologically antagonize the effects of acetylcholine and therefore its reported atrial antiarrhythmic properties cannot be explained by muscarinic receptor blockade.
托西溴苄铵的抗纤颤特性最初是在实验性心房颤动中观察到的，但尚未探究该现象的细胞基础。本研究的目的是确定在有无胆碱能影响的情况下，托西溴苄铵对豚鼠心房肌的电生理特性。托西溴苄铵（10^(-6) M - 10^(-4) M）使心房动作电位时程呈浓度依赖性延长，阈浓度为10^(-5) M。普萘洛尔（10^(-6) M）阻断β肾上腺素能受体或酚妥拉明（10^(-6) M）阻断α肾上腺素能受体均未改变托西溴苄铵的这种直接作用。在第二系列实验中，测定了托西溴苄铵的毒蕈碱受体阻断特性。乙酰胆碱使起搏（200毫秒）的左心房肌条动作电位时程呈浓度依赖性缩短。在存在托西溴苄铵（10^(-6) M - 10^(-3) M）的情况下，这种公认的毒蕈碱样作用未改变。这些数据表明，托西溴苄铵在生理上对心房肌有直接作用，可延长动作电位时程。该化合物似乎在生理上并不拮抗乙酰胆碱的作用，因此其报道的心房抗心律失常特性不能用毒蕈碱受体阻断来解释。
