Effect of clobenpropit, a centrally acting histamine H3-receptor antagonist, on electroshock- and pentylenetetrazol-induced seizures in mice
Effect of clobenpropit, a centrally acting histamine H3-receptor antagonist, on electroshock- and pentylenetetrazol-induced seizures in mice
复制标题
DOI：
10.1007/s007020050081
复制
发表时间：
1998
影响因子：
3.3
通讯作者：
W. Fischer;H. van der Goot
中科院分区：
文献类型：
--
作者：
W. Fischer;H. van der Goot
在两种典型的小鼠癫痫发作模型中研究了Clobenpropit（组胺的异噻唑烷衍生物和有效的H3受体拮抗剂）的抗惊厥活性。在最大电休克癫痫发作阈值试验中，clobenpropit剂量依赖性地提高强直性（后肢伸展）癫痫发作的电惊厥阈值，但仅在40 mg/kg i. p.的高剂量下确定了约15%的显著增加。immepip和（R）-α-甲基组胺（选择性H3受体激动剂）降低了该药物的保护作用。在与两种标准抗癫痫药联合用药时，氯苯丙酸（20和40 mg/kg）显著增加了卡马西平的抗惊厥有效性，并倾向于增加丙戊酸盐的有效性。进一步的研究表明，高剂量的氯苄丙酸也显着增加血浆卡马西平浓度。另一方面，在南卡罗来纳州。PTZ癫痫发作阈值测试clobenpropit显示没有保护作用。在旋转杆共济失调试验中，在80 mg/kg氯苯丙酸时观察到运动功能受损。总之，目前的研究结果表明，氯苯丙酸对全身强直性发作以及阵挛性发作没有明显的抗惊厥作用。
The anticonvulsant activity of clobenpropit, an isothiourea derivative of histamine and potent H3-receptor antagonist, was investigated in two representative seizure models in mice. In the maximal electroshock seizure threshold test, clobenpropit dose-dependently raised the electroconvulsive threshold for tonic (hindlimb extension) seizures, but a significant increase of about 15% was determined only at the high dose of 40 mg/kg i.p. The protective action of this drug was reduced by immepip and (R)-α-methylhistamine, selective H3-receptor agonists. In co-medication with two standard antiepileptics, clobenpropit (20 and 40 mg/kg) significantly increased the anticonvulsant effectiveness of carbamazepine and tended to increase the effectiveness of valproate. Additional studies indicated that the high dose of clobenpropit also significantly enhanced the plasma carbamazepine concentration. One the other hand, in the s.c. PTZ seizure threshold test clobenpropit revealed no protective effects. In the rotarod ataxia test, impaired motor function was observed at 80 mg/kg clobenpropit. In conclusion, the present findings indicated no pronounced anticonvulsant effects of clobenpropit against generalized tonic as well as clonic seizures.