Effect of clobenpropit on regional cerebral blood flow in rat hippocampus  

Clobenpropit改善大鼠海马局部脑血流的作用(英文)

作　　者：陈忠[1] 

机构地区：[1]浙江大学医学院基础医学系药理学研究室,杭州中国310031

出　　处：《Acta Pharmacologica Sinica》2001年第4期69-74,共6页中国药理学报（英文版）

基　　金：Project partly supported by the Scientific Funds of CAO Guang-Biao in Zhejiang University.

摘　　要：AIM: The effect of clobenpropit on regional cerebral blood flow (rCBF) was investigated in the rat hippocampus. METHODS: rCBF was determined in the hippocampus by the hydrogen clearance method. The blood pressure was measured by a tail-cuff plethysmograph. RESULTS: Intracerebroventricular (icv) injection of clobenpropit (20, 50 μg), a representative H3-antago-nist, dose-dependently and significantly increased rCBF in the hippocampus. The increase of rCBF induced by clobenpropit was enhanced by metoprine (1,2 mg/kg), a selective histamine N-methyltransferase inhibitor; however, was antagonized by an H3-agonist, (R)-α-methyl-histamine (5 μg), an H1-antagonist, mepyramine (5 - 10 mg/kg), and an H2-antagonist, zolantidine (10 mg/ kg). Clobenpropit caused no apparent effects on blood pressure even at a high dose of 50 μg. CONCLUSION : These results suggest that brain endogenous histamine may contribute to increase rCBF in the rat hippocampus via both the post-synaptic H1-, H2-receptors and the pre-synaptic H3-receptor.目的:研究和阐明clobenpropit对大鼠海马局部脑血流(rCBF)的作用机制。方法:采用氢清除法测定海马的局部脑血流,并利用大鼠尾部体积描记器测定大鼠的血压。结果:侧脑室内注射clobenpropit(20,50μg)后,15-30min,可剂量依赖性、显著地改善8-16月龄大鼠海马中的rCBF,而且clobenpropit的作用可被氯苯氨啶加强。(R)-α-甲基组胺(5μg)则明显抑制clobenpropit的rCBF改善作用。另外,美吡拉敏(5,10mg/kg)和zolantidine(10mg/kg)均可剂量依赖性地抑制clobenpropit提高rCBF的作用。Clobenpropit(5-50μg)对血压不产生影响。结论:Clobenpropit可以改善8-16月龄大鼠海马中rCBF,其作用主要与组胺H_1,H_2和H_3受体相关。

关 键 词：CLOBENPROPIT histamine H3 receptors metopnne METHYLHISTAMINES 

分 类 号：R96[医药卫生—药理学]