Local anesthetic properties of calcium channel blockers

钙通道阻滞剂的局部麻醉特性

• 批准号: 6340057
• 负责人: MUSTAFA G MUJTABA
• 金额: $ 1.42万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-05-01 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6340057
• 关键词: calcium channel blockers; drug interactions; drug receptors; laboratory rat; local anesthetics; neuropharmacology; proprioception /kinesthesia; protein structure function; psychomotor function; psychopharmacology; site directed mutagenesis; sodium channel; voltage gated channel

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.

描述（申请人的逐字描述）摘要）本研究的目的是 该应用是为了加深我们对局部麻醉剂的理解， 电压门控钠通道药理学通过使用钙通道阻滞剂作为 独特的分子探针这项研究从对钠的详细评估开始 钙通道阻滞剂的通道亲和力与已知的局部 麻醉剂初步数据表明，钙通道阻滞剂可能结合 已知的局部麻醉部位，其中一些药物阻断钠电流 比普通的局部麻醉剂如布比卡因更有效。戊二胺a 钙通道阻滞剂，在31.LM是一种有效的使用依赖性阻滞剂， 人体心脏钠离子通道在重复脉冲。存在显著 用于休息和钙失活山通道的补品块 通道阻滞剂。此外，来自在坐骨神经注射的大鼠的体内数据 神经部位与异戊烯胺表明，一些钙通道阻滞剂可能有 比长效局部阻滞剂更长的伤害性、本体感受性和运动阻滞 麻醉剂，如布比卡因，今天在诊所使用。因此 AIM 1概述的实验将确定静息/失活 神经元和心脏钠通道的亲和力，以及绘制出 这些通道上的钙通道阻滞剂的受体位点。实验 旨在评估钙的可能临床益处 通道阻滞剂在大鼠坐骨神经上的体内作用。