Oishi R, Nishibori M, Itoh Y, Saeki K
Eur J Pharmacol. 1986 May 27;124(3):337-42. doi: 10.1016/0014-2999(86)90236-0.
The effect of diazepam on brain histamine turnover was examined in mice. The steady state levels of histamine and tele-methylhistamine remained unchanged following the i.p. administration of 0.2-20 mg/kg of diazepam. However, diazepam in doses over 5 mg/kg significantly decreased histamine turnover, as estimated from the accumulation of tele-methylhistamine after pargyline treatment. Other benzodiazepines such as chlordiazepoxide, nitrazepam and estazolam in high doses also decreased histamine turnover. The inhibitory effect of diazepam on histamine turnover was antagonized by the pretreatment with a benzodiazepine antagonist Ro 15-1788. The histamine turnover was significantly inhibited by 2 mg/kg of muscimol. Diazepam (0.2-1 mg/kg) markedly and dose-dependently potentiated the inhibitory effect of 1 mg/kg of muscimol from non-significant to highly significant levels. The potentiation by diazepam was also antagonized by Ro 15-1788. Therefore, diazepam probably decreases histamine turnover in the brain via the benzodiazepine-GABA receptor complex.
研究了地西泮对小鼠脑内组胺代谢周转的影响。腹腔注射0.2 - 20mg/kg地西泮后，组胺和甲基组胺的稳态水平保持不变。然而，剂量超过5mg/kg的地西泮显著降低了组胺代谢周转，这是根据帕吉林处理后甲基组胺的积累来估计的。其他苯二氮䓬类药物如氯氮卓、硝西泮和艾司唑仑高剂量时也降低了组胺代谢周转。地西泮对组胺代谢周转的抑制作用可被苯二氮䓬类拮抗剂Ro 15 - 1788预处理所拮抗。2mg/kg的蝇蕈醇显著抑制了组胺代谢周转。地西泮（0.2 - 1mg/kg）显著且剂量依赖性地增强了1mg/kg蝇蕈醇的抑制作用，使其从无显著作用增强到高度显著水平。地西泮的这种增强作用也被Ro 15 - 1788所拮抗。因此，地西泮可能通过苯二氮䓬 - GABA受体复合物降低脑内组胺代谢周转。
