Local anesthetic properties of calcium channel blockers

(申请人逐字描述？S摘要)研究目的 这项申请是为了加深我们对局麻药和 钙通道阻滞剂的电压门控性钠通道药理作用 独特的分子探测器。这项研究开始于对钠的详细评估 钙通道阻滞剂的通道亲和力与已知局部的比较 麻醉剂。初步数据表明，钙通道阻滞剂可能与 已知的局部麻醉部位，其中一些药剂阻断钠电流 比布比卡因等常见的局部麻醉剂更有效。丙胺，一种 钙通道阻滞剂，At 31。LM是一种有效的使用依赖阻滞剂。 人在重复脉搏期间的心脏钠通道。有重要意义的是 补钙补药安神止血止血药 通道阻滞剂。此外，从大鼠坐骨神经注射的体内数据 丙胺的神经部位提示一些钙通道阻滞剂可能有 比起长效局部作用更长的伤害性、本体感和运动阻滞 麻醉剂，如布比卡因，今天在临床上使用。因此， 为AIM1概述的实验将确定休眠/停用 神经元和心脏钠通道的亲和力以及绘制 钙通道阻滞剂在这些通道上的受体位置。实验 在AIM2中设计用于评估钙的可能临床益处 体内通道阻滞剂对大鼠坐骨神经的作用。

DESCRIPTION (Verbatim from the applicant?s abstract) The research objective of this application is to further our understanding of local anesthetics and voltage-gated sodium channel pharmacology by using calcium channel blockers as unique molecular probes. The study begins with a detailed evaluation of sodium channel affinities for calcium channel blockers in comparison with known local anesthetics. Preliminary data indicate that calcium channel blockers may bind to known local anesthetic sites, and some of these agents block sodium current more potently than common local anesthetics such as bupivacaine. Prenylamine, a calcium channel blocker, at 31.LM is an effective use-dependent blocker of human cardiac sodium channels during repetitive pulses. There is significant tonic block for resting and for inactivated hill channels by the calcium channel blockers. Furthermore, in vivo data from rats injected at the sciatic nerve site with prenylamine suggest that some calcium channel blockers may have longer nociceptive, proprioceptive, and motor block than the long-acting local anesthetics, such as bupivacaine, used today in the clinics. Thus, the experiments outlined for AIM1 will determine the resting/ inactivated affinities of neuronal and cardiac sodium channels as well as mapping out the receptor sites on these channels for the calcium channel blockers. Experiments in AIM2 are designed to evaluate the possible clinical benefits of calcium channel blockers in vivo on rat sciatic nerves.