Dubray C, Boucher M, Paire M, Pinatel H, Duchêne-Marullaz P
J Cardiovasc Pharmacol. 1986 Nov-Dec;8(6):1229-34. doi: 10.1097/00005344-198611000-00020.
In animals and humans, the antiarrhythmic agent disopyramide is primarily metabolized by mono-N-dealkylation. The effects of disopyramide and its N-dealkylated metabolite (MND) were investigated in 13 conscious dogs with chronic atrioventricular (A-V) block and implanted atrial pacing electrodes. Our data clearly show that both compounds used within the therapeutic plasma level range induced lengthening of the atrial effective refractory period (AERP) as reflected by the diminution of the maximal atrial frequency determined by pacing. However, at equivalent drug plasma concentrations, disopyramide induced a more marked decrease (1.2-1.7 times) in the maximal atrial frequency than did its metabolite. Both compounds increased mean arterial pressure (MAP) and atrial rate and decreased ventricular rate, but the effects on MAP and atrial rate were more marked with disopyramide than with MND. Thus, with regard to these cardiovascular parameters, the parent drug and MND possess distinct pharmacodynamic profiles, which may in part be related to their respective vagolytic power.
在动物和人类中，抗心律失常药物丙吡胺主要通过单-N-脱烷基化进行代谢。在13只患有慢性房室（A-V）传导阻滞并植入心房起搏电极的清醒犬中，研究了丙吡胺及其N-脱烷基代谢产物（MND）的作用。我们的数据清楚地表明，在治疗性血浆水平范围内使用的这两种化合物均会导致心房有效不应期（AERP）延长，这通过起搏测定的最大心房频率降低得以体现。然而，在等效的药物血浆浓度下，丙吡胺比其代谢产物引起的最大心房频率降低更为显著（1.2 - 1.7倍）。两种化合物均使平均动脉压（MAP）和心房率升高，并使心室率降低，但丙吡胺对MAP和心房率的影响比MND更为显著。因此，就这些心血管参数而言，母体药物和MND具有不同的药效学特征，这可能部分与其各自的抗迷走神经作用强度有关。
