Lawson J W
Arch Int Pharmacodyn Ther. 1984 Jul;270(1):106-15.
Quinidine coadministered with propranolol produces antiarrhythmic potentiation. The mechanism is uncertain although some in vitro electrophysiologic studies have suggested that it may be due to propranolol-induced cardiac beta receptor blockade. Other effects of propranolol, however, including a decrease in cardiac sympathetic nerve activity as well as some direct cardiac membrane effects might also contribute. The possible contributions of these effects were studied indirectly by coadministering quinidine with several compounds (d-propranolol, l-propranolol, d-practolol, practolol, pronethalol, and phenytoin) which have varying effects on these parameters. Antiarrhythmic activity was determined as protection against chloroform-induced ventricular arrhythmias and beta blockade as inhibition of isoproterenol-induced tachycardia. Only d- and l-propranolol and phenytoin potentiated quinidine. The d-isomer was only approximately 1/8th as potent as the l-isomer for inhibiting isoproterenol tachycardia, and the lowest dose of the d-isomer coadministered with quinidine produced antiarrhythmic potentiation but little if any inhibition of isoproterenol tachycardia. The results suggest that cardiac beta blockade alone does not adequately explain the potentiation of quinidine by propranolol in the mouse. Perhaps a decrease in cardiac sympathetic nerve activity and the direct membrane effects as occur with d-, l-, and d,l-propranolol and phenytoin may also contribute to the potentiation.
奎尼丁与普萘洛尔合用可产生抗心律失常增效作用。尽管一些体外电生理研究表明其机制可能是普萘洛尔诱导的心脏β受体阻滞，但具体机制尚不确定。然而，普萘洛尔的其他作用，包括心脏交感神经活性降低以及一些直接的心脏膜效应也可能起作用。通过将奎尼丁与几种对这些参数有不同影响的化合物（d-普萘洛尔、l-普萘洛尔、d-普拉洛尔、普拉洛尔、萘心安和苯妥英）合用，间接研究了这些作用的可能贡献。抗心律失常活性通过预防氯仿诱导的室性心律失常来确定，β受体阻滞通过抑制异丙肾上腺素诱导的心动过速来确定。只有d-和l-普萘洛尔以及苯妥英能增强奎尼丁的作用。d-异构体抑制异丙肾上腺素心动过速的效力仅约为l-异构体的1/8，与奎尼丁合用的d-异构体最低剂量可产生抗心律失常增效作用，但对异丙肾上腺素心动过速几乎没有抑制作用。结果表明，仅心脏β受体阻滞不足以解释普萘洛尔在小鼠中对奎尼丁的增效作用。也许d-、l-和d,l-普萘洛尔以及苯妥英所产生的心脏交感神经活性降低和直接膜效应也可能有助于增效作用。
