Gupta M, Kulkarni S K
Pharmacology Division, University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh, 160 014, India.
Indian J Exp Biol. 2000 Apr;38(4):332-7.
L-Deprenyl (Selegeline) introduced for use in parkinson's disease, is implicated to show beneficial effects in epilepsy, alzheimer's disease, cognition, depression and other age related neurological diseases. In this study, we investigated the CNS effects of L-deprenyl with special reference to epilepsy, anxiety and cognition and memory in mice. L-deprenyl (10, 20 and 40 mg/kg) showed a significant anticonvulsant activity against pentylenetetrazole (PTZ)-induced convulsions. Combination of L-deprenyl (10 mg/kg) with the sub-protective dose of diazepam (1 mg/kg) showed potentiation of the anticonvulsant effect. In the maximal-electroshock (MES)-induced convulsions, L-deprenyl (10 mg/kg) significantly delayed the onset and decreased the duration of extensor phase. Its combination with the lower dose of phenytoin (10 mg/kg) showed potentiation in response compared to the per se effect of both the drugs. However, L-deprenyl did not show any protective effect in lithium-pilocarpine induced status epilepticus. Acute treatment with L-deprenyl had no effect on learning and memory. In chronic treatment, L-deprenyl per se showed no effect on learning and memory but did improve the condition in mice with scopolamine induced memory deficit. L-Deprenyl per se was anxiogenic though in combination with diazepam (1 mg/kg) it potentiated the antianxiety effect of the latter. The above observations suggest that in epilepsy, L-deprenyl might be acting partially by influencing the GABAA/benzodiazepine mechanism in the brain (similar to diazepam and phenytoin), and in cognition enhancing effect, the cholinergic system might be playing a role. Thus, L-deprenyl could prove to be an adjuvant in the antiepileptic therapy and beneficial in dementia associated with epilepsy.
用于帕金森病治疗的L-司来吉兰(Selegeline),被认为在癫痫、阿尔茨海默病、认知、抑郁及其他与年龄相关的神经疾病中具有有益作用。在本研究中,我们特别针对癫痫、焦虑以及小鼠的认知与记忆,研究了L-司来吉兰对中枢神经系统的影响。L-司来吉兰(10、20和40毫克/千克)对戊四氮(PTZ)诱导的惊厥显示出显著的抗惊厥活性。L-司来吉兰(10毫克/千克)与亚保护剂量的地西泮(1毫克/千克)联合使用,显示出抗惊厥作用的增强。在最大电休克(MES)诱导的惊厥中,L-司来吉兰(10毫克/千克)显著延迟了发作起始并缩短了伸肌期的持续时间。与苯妥英钠较低剂量(10毫克/千克)联合使用时,与两种药物单独使用相比,反应增强。然而,L-司来吉兰在锂-匹罗卡品诱导的癫痫持续状态中未显示出任何保护作用。L-司来吉兰急性治疗对学习和记忆没有影响。在慢性治疗中,L-司来吉兰本身对学习和记忆没有影响,但确实改善了东莨菪碱诱导的记忆缺陷小鼠的状况。L-司来吉兰本身具有致焦虑作用,不过与地西泮(1毫克/千克)联合使用时,可增强后者的抗焦虑作用。上述观察结果表明,在癫痫中,L-司来吉兰可能部分通过影响大脑中的GABAA/苯二氮䓬机制(类似于地西泮和苯妥英钠)发挥作用,而在认知增强作用方面,胆碱能系统可能发挥作用。因此,L-司来吉兰可能被证明是抗癫痫治疗中的一种辅助药物,对与癫痫相关的痴呆有益。