Gogas K R, Hough L B
Department of Pharmacology and Toxicology, Albany Medical College, New York.
J Pharmacol Exp Ther. 1989 Jan;248(1):262-7.
In order to test directly the hypothesis that brain histamine and H2-receptors mediate the naloxone-resistant footshock-induced antinociception (FSIA) elicited by 3 min of 3.5 mA, the effect of i.c.v. H2-antagonists on this response was determined. Intracerebroventricular zolantidine dimaleate produced an inhibition of the response that was both time- and dose-dependent, with no effect on base-line responses. A dose of 20 micrograms produced maximal (93%) inhibition of FSIA when given 10 min before footshock, with a calculated ID50 of 7.18 nmol. Eight additional H2-antagonists with varying structures and brain-penetrating qualities also exhibited dose-dependent inhibition of the response with no effect on base-line nociception. The potencies of these compounds for inhibition of naloxone-resistant FSIA correlated significantly (r = 0.966, P less than .001; rho = 0.980, P less than .002) with their affinities at the H2-receptor, providing strong support for the hypothesis that brain histamine and H2-receptors are important components of naloxone-resistant FSIA.
为了直接验证脑内组胺和H2受体介导由3.5 mA的电流刺激3分钟所引发的纳洛酮抵抗性足部电击诱导的抗伤害感受（FSIA）这一假说，研究了脑室内注射H2拮抗剂对此反应的影响。脑室内注射马来酸佐兰替丁对该反应产生了时间和剂量依赖性的抑制作用，对基线反应无影响。在足部电击前10分钟给予20微克的剂量可产生最大（93%）的FSIA抑制作用，计算得出的半数抑制剂量（ID50）为7.18纳摩尔。另外八种具有不同结构和脑穿透特性的H2拮抗剂也表现出剂量依赖性的反应抑制，对基线伤害感受无影响。这些化合物抑制纳洛酮抵抗性FSIA的效力与其在H2受体上的亲和力显著相关（r = 0.966，P <.001；rho = 0.980，P <.002），为脑内组胺和H2受体是纳洛酮抵抗性FSIA的重要组成部分这一假说提供了有力支持。
