Roeske W R, Lee H R, Yamamura H I, Schoemaker H
Adv Myocardiol. 1985;6:71-82.
In this study, we demonstrate the in vivo labeling by [3H]nitrendipine ([3H]NTD) of peripheral tissues and the brain in Sprague-Dawley rats. Specific binding is decreased in a dose-dependent manner by nifedipine, with a mean inhibitory dose of 2-10 mg/kg (i.p.). Thin-layer chromatography of the particulate-bound radioactivity reveals that the predominant tritiated drug bound in the left ventricle and the cerebral cortex is [3H]NTD, whereas metabolites constitute the main species in the liver. Peak radioactivity is seen at 15 min following an intravenous injection of [3H]NTD. Highly perfused tissues such as the heart, brain, and lung have significant [3H]NTD binding. In contrast to previously reported in vitro studies, [3H]NTD binding is low in the aorta, skeletal muscle, and ileum. This in vivo animal model is suitable for pharmacokinetic and physiological studies of the calcium channel in intact animals.
在本研究中，我们证明了用[3H]尼群地平（[3H]NTD）对Sprague-Dawley大鼠的外周组织和脑进行体内标记。硝苯地平以剂量依赖方式降低特异性结合，平均抑制剂量为2 - 10 mg/kg（腹腔注射）。对颗粒结合放射性进行的薄层色谱分析表明，左心室和大脑皮质中结合的主要氚标记药物是[3H]NTD，而肝脏中的主要成分是代谢物。静脉注射[3H]NTD后15分钟出现放射性峰值。心脏、脑和肺等高灌注组织具有显著的[3H]NTD结合。与先前报道的体外研究相反，[3H]NTD在主动脉、骨骼肌和回肠中的结合较低。这种体内动物模型适用于完整动物体内钙通道的药代动力学和生理学研究。
