Sakai N, Onodera K, Maeyama K, Yanai K, Watanabe T
Department of Pharmacology I, School of Medicine, Tohoku University, Sendai, Japan.
Life Sci. 1991;48(25):2397-404. doi: 10.1016/0024-3205(91)90373-j.
The purpose of this study was to examine the effects of thioperamide, a histamine H3 antagonist, on the locomotor activity and the brain histamine content in mast-cell-deficient W/Wv mice. Thioperamide (12.5 and 25 mg/kg) showed significant increase in the locomotor activity of W/Wv mice, measured by a photo-beam system, 1 hr after the intraperitoneal injection. However, more than 75 mg/kg of thioperamide showed not only the reduction of the locomotor activity but also the inhibition of motor coordination measured by the rotarod performance. The increase in the locomotor activity by thioperamide was blocked by i. p. pretreatment with (R)-alpha-methyl-histamine, an H3 agonist, or pyrilamine, an H1 antagonist, or zolantidine, an H2 antagonist. The brain histamine content was decreased by thioperamide (12.5-75.0 mg/kg), 1 hr after administration. Thus, the blockade of histamine H3 receptor by thioperamide showed the activation of locomotor activity of mice, which may be mediated by H1 and/or H2 receptors. The present data support the hypothesis that central histaminergic neurons may be involved in the control of state of wakefulness.
本研究的目的是考察组胺H3拮抗剂硫代哌酰胺对肥大细胞缺陷型W/Wv小鼠运动活性及脑组胺含量的影响。通过光束系统测定，腹腔注射后1小时，硫代哌酰胺（12.5和25mg/kg）使W/Wv小鼠的运动活性显著增加。然而，硫代哌酰胺剂量超过75mg/kg时，不仅运动活性降低，还会抑制通过转棒试验测定的运动协调性。硫代哌酰胺引起的运动活性增加被H3激动剂（R）-α-甲基组胺、H1拮抗剂吡苄明或H2拮抗剂佐兰丁腹腔预处理所阻断。给药1小时后，硫代哌酰胺（12.5 - 75.0mg/kg）使脑组胺含量降低。因此，硫代哌酰胺对组胺H3受体的阻断显示出对小鼠运动活性的激活作用，这可能由H1和/或H2受体介导。目前的数据支持中枢组胺能神经元可能参与觉醒状态控制这一假说。
