Miyazaki S, Onodera K, Imaizumi M, Timmerman H
Biology Laboratory, Research & Development Division, Yamasa Corporation, Choshi, Chiba, Japan.
Life Sci. 1997;61(4):355-61. doi: 10.1016/s0024-3205(97)00406-2.
The effects of clobenpropit (VUF-9153), a potent histamine H3-receptor antagonist, on a scopolamine-induced learning deficit in the step-through passive avoidance test was studied in mice. Clobenpropit (10 and 20 mg/kg) alone showed a tendency to ameliorate the scopolamine-induced learning deficit, and clobenpropit (10 mg/kg) in combination with zolantidine (20 mg/kg), a histamine H2-receptor antagonist, ameliorated the scopolamine-induced effect. This ameliorating effect was antagonized by (R)-alpha-methylhistamine (20 mg/kg), a histamine H3-receptor agonist and pyrilamine (20 mg/kg), a histamine H1-receptor antagonist, suggesting that clobenpropit in combination with zolantidine showed the ameliorating effect via histamine H3 receptors and/or histamine H1 receptors. We also studied the effects of clobenpropit on cholinergic and monoaminergic systems. Clobenpropit did not show any significant effect on these neuronal systems except the activation of noradrenergic system. The present results suggest that the effect of clobenpropit might be partially involved with the activation of noradrenergic system, and the histaminergic system may play certain important roles in learning and memory.
在小鼠中研究了强效组胺H3受体拮抗剂氯苯丙哌（VUF-9153）对东莨菪碱诱导的跳台被动回避试验学习缺陷的影响。单独使用氯苯丙哌（10和20mg/kg）显示出改善东莨菪碱诱导的学习缺陷的趋势，并且氯苯丙哌（10mg/kg）与组胺H2受体拮抗剂佐兰替丁（20mg/kg）联合使用可改善东莨菪碱诱导的效应。这种改善作用被组胺H3受体激动剂（R）-α-甲基组胺（20mg/kg）和组胺H1受体拮抗剂吡拉明（20mg/kg）拮抗，表明氯苯丙哌与佐兰替丁联合使用通过组胺H3受体和/或组胺H1受体显示出改善作用。我们还研究了氯苯丙哌对胆碱能和单胺能系统的影响。除了激活去甲肾上腺素能系统外，氯苯丙哌对这些神经元系统没有显示出任何显著影响。目前的结果表明，氯苯丙哌的作用可能部分与去甲肾上腺素能系统的激活有关，并且组胺能系统可能在学习和记忆中起某些重要作用。
