Antinociceptive effects of intrathecally injected cholinomimetic drugs in the rat and cat.
Antinociceptive effects of intrathecally injected cholinomimetic drugs in the rat and cat.
复制标题
鞘内注射拟胆碱药物对大鼠和猫的镇痛作用。
DOI：
10.1016/0014-2999(85)90474-1
复制
发表时间：
1985
影响因子：
5
通讯作者：
Harty,GJ
中科院分区：
文献类型：
--
作者：
Yaksh,TL;Dirksen,R;Harty,GJ
长期植入鞘内导管的大鼠表现出热板反应潜伏期和甩尾反应潜伏期的剂量依赖性增加，并降低了通过留置导管向蛛网膜下腔注射某些类胆碱素后扭体反应的幅度。这些药剂的构效关系为：氧托莫林和GT；卡巴胆碱和GT；乙酰胆碱+毒扁豆碱；⋙乙酰胆碱=尼古丁-盐酸=0。阿托品而不是纳洛酮、士的宁、印防己毒素、咖喱或亚甲基脲和酚妥拉明逆转了这种抗伤害作用。这提示M胆碱能机制参与了这一过程。将卡巴胆碱注入装有鞘内导管的猫的脊髓蛛网膜下腔的实验也显示了一种有效的抗伤害作用，该作用可被阿托品完全拮抗。这种影响在躯体上是有限的，由离导管末端最近的脊髓节段支配的皮肤表面显示出最显着的影响和最短的起效潜伏期。这一观察结果，加上全身反射运动功能或姿势控制没有改变，进一步表明鞘内小剂量给药后M受体激动剂的选择性脊髓有效性。
Rats chronically implanted with intrathecal catheters displayed a dose-dependent increase in the hot-plate, tail-flick response latencies, and decreased the magnitude of the writhing response following the injection of certain cholinomimetics into the subarachnoid space through the indwelling catheter. The structure-activity relationship for these agents is oxotremorine> carbachol> acetylcholine+ physostigmine⋙ acetylcholine= nicotine-HCL= 0. Atropine but not naloxone, strychnine, picrotoxin, curare or methysegride and phentolamine, reversed the antinociceptive effect. This suggests the involvement of muscarinic cholinergic mechanisms. Experiments with intrathecal injection of carbachol into the spinal subarachnoid space of cats fitted with intrathecal catheters also revealed a potent antinociceptive effect which was completely antagonized by atropine. The effect was somatotopically limited with the skin surfaces innervated by cord segments nearest the catherer tip showing the most significant effect with the shortest latency of onset. This observation, together with the absence of changes in general reflex motor function or postural control further indicated a selective spinal effectiveness of muscarinic agonists after low dose intrathecal administration.