Suzuki T, Takamori K, Takahashi Y, Narita M, Misawa M, Onodera K
Department of Pharmacology, School of Pharmacy, Hoshi University, Tokyo, Japan.
Life Sci. 1994;54(3):203-11. doi: 10.1016/0024-3205(94)00589-3.
The effects of thioperamide, an H3 antagonist, and histamine H1 and H2 antagonists (s.c.) on morphine (s.c. or i.c.v.)- and U-50,488H (i.c.v.)-induced antinociception in male ddY mice were examined using the hot-plate (55 degrees C) test. Thioperamide significantly inhibited morphine-induced antinociception, but not U-50,488H-induced antinociception. The suppressive effect of thioperamide on morphine-induced antinociception was reversed by the H1 antagonist pyrilamine, but not by the H2 antagonist zolantidine. On the other hand, pyrilamine significantly potentiated the antinociception induced by morphine, but not that induced by U-50,488H. Zolantidine significantly inhibited morphine-induced antinociception in a dose-dependent manner, but not U-50,488H-induced antinociception. Both astemizole, an H1 antagonist, and ranitidine, an H2 antagonist, which are known to barely cross the blood brain barrier, did not affect morphine-induced antinociception. These results suggest that morphine-induced antinociception may be potentiated by activation of H2 receptors and suppressed by activation of H1 receptors in the brain. Furthermore, neuronal histamine release induced by thioperamide may suppress morphine-induced antinociception through H1 receptors.
使用热板（55摄氏度）试验，研究了H3拮抗剂硫代哌酰胺以及组胺H1和H2拮抗剂（皮下注射）对雄性ddY小鼠中吗啡（皮下或脑室内注射）和U-50,488H（脑室内注射）诱导的抗伤害感受的影响。硫代哌酰胺显著抑制吗啡诱导的抗伤害感受，但不抑制U-50,488H诱导的抗伤害感受。硫代哌酰胺对吗啡诱导的抗伤害感受的抑制作用可被H1拮抗剂吡苄明逆转，但不能被H2拮抗剂佐兰替丁逆转。另一方面，吡苄明显著增强吗啡诱导的抗伤害感受，但不增强U-50,488H诱导的抗伤害感受。佐兰替丁以剂量依赖性方式显著抑制吗啡诱导的抗伤害感受，但不抑制U-50,488H诱导的抗伤害感受。已知几乎不能穿过血脑屏障的H1拮抗剂阿司咪唑和H2拮抗剂雷尼替丁均不影响吗啡诱导的抗伤害感受。这些结果表明，吗啡诱导的抗伤害感受可能通过大脑中H2受体的激活而增强，通过H1受体的激活而受到抑制。此外，硫代哌酰胺诱导的神经元组胺释放可能通过H1受体抑制吗啡诱导的抗伤害感受。
