Wang J, Carpentier R G
Department of Physiology and Biophysics, College of Medicine, Howard University, Washington, DC 20059.
Int J Cardiol. 1994 Oct;46(3):235-42. doi: 10.1016/0167-5273(94)90246-1.
We studied the in-vitro electrophysiologic effects of equimolar concentrations of cocaine and its metabolites on rat cardiac tissues. The effects on the sinus node rate were studied in spontaneously active sinoatrial preparations. The order of magnitude of the effects was: ethylcocaine > cocaine > benzoylecgonine and ecgonine methyl ester > ecgonine. The effects of cocaine and ethylcocaine were not additive. The actions of cocaine and ethylcocaine on membrane potentials were studied in papillary muscles driven at 5 Hz. Both compounds depressed to similar degrees the resting potential and the amplitude of the action potential, and increased the duration of the action potential. Simultaneous exposure to the two drugs did not result in effects greater than those of ethylcocaine or cocaine alone. It is concluded that (a) cocaine and its metabolites depressed the sinus node rate. Only cocaine and ethylcocaine exerted actions that may be of clinical significance. (b) Ethylcocaine had an effect greater than that of cocaine on the sinus node rate, and similar to that of the parent compound on ventricular membrane potentials. Thus, ethylcocaine may play a significant role in the cardiac electrophysiologic actions of cocaine, when the latter is used in combination with ethanol. (c) The effects of cocaine and ethylcocaine were not additive.
我们研究了等摩尔浓度的可卡因及其代谢产物对大鼠心脏组织的体外电生理效应。在自发活动的窦房结标本中研究了对窦房结速率的影响。效应的量级顺序为：乙基可卡因＞可卡因＞苯甲酰芽子碱和芽子碱甲酯＞芽子碱。可卡因和乙基可卡因的效应并非相加性的。在以5赫兹驱动的乳头肌中研究了可卡因和乙基可卡因对膜电位的作用。两种化合物对静息电位和动作电位幅度的抑制程度相似，并增加了动作电位的持续时间。同时暴露于这两种药物并未产生比单独使用乙基可卡因或可卡因更大的效应。得出以下结论：（a）可卡因及其代谢产物降低了窦房结速率。只有可卡因和乙基可卡因产生了可能具有临床意义的作用。（b）乙基可卡因对窦房结速率的影响大于可卡因，且对心室膜电位的影响与母体化合物相似。因此，当可卡因与乙醇联合使用时，乙基可卡因可能在可卡因的心脏电生理作用中起重要作用。（c）可卡因和乙基可卡因的效应并非相加性的。
