Gusel' V A, Vlasov G P, Vol'f N L, Kozhevnikova N Iu, Ferdman L A
Farmakol Toksikol. 1985 Jul-Aug;48(4):28-31.
It has been shown in chronic experiments on rabbits with electrochemoelectrodes implanted into the dorsal hippocamp that the first administration of met-enkephalin in a dose of 60 to the hippocamp induced the development of an epileptogenic focus (EF) or potentiated the action of the penicillin-induced EF. The second administration of met-enkephalin in the same dose to the hippocamp (interval in a standard scheme of experiments 5 days) did not lead to the production of the EF, which attests to rapid development of tolerance to the epileptizing action of the peptide, with this tolerance being preserved for 20 subsequent days of observation over the animals. After tolerance developed, administration of 60 micrograms met-enkephalin 5 to 10 min before penicillin produced an antiepileptic action, thereby preventing the development of the EF. Met-enkephalin (0.1 and 1 microgram) did not epileptize hippocampal neurons but lowered the action of the penicillin-induced EF after the development of tolerance to the epileptizing action of a large dose of the peptide. The animals did not develop tolerance to the antiepileptic effect of met-enkephalin. The data obtained confirm the hypothesis that different opiate receptors are responsible for the epileptizing (delta-receptors) and antiepileptic (mu-receptors) action of the enkephalin. The effect of small doses of met-enkephalin appears to mirror to a greater degree the involvement of endogenous enkephalins in the epileptogenesis.
在对植入背侧海马体电化学电极的兔子进行的慢性实验中发现，首次向海马体注射剂量为60微克的甲硫氨酸脑啡肽会诱发致痫灶（EF）的形成，或增强青霉素诱发的EF的作用。以相同剂量再次向海马体注射甲硫氨酸脑啡肽（在标准实验方案中的间隔时间为5天）并未导致EF的产生，这证明对该肽的致痫作用迅速产生了耐受性，在随后对动物进行观察的20天里这种耐受性一直存在。在耐受性形成后，在注射青霉素前5至10分钟给予60微克甲硫氨酸脑啡肽会产生抗癫痫作用，从而防止EF的形成。甲硫氨酸脑啡肽（0.1微克和1微克）不会使海马体神经元发生癫痫发作，但在对大剂量该肽的致痫作用产生耐受性后，会降低青霉素诱发的EF的作用。动物对甲硫氨酸脑啡肽的抗癫痫作用未产生耐受性。所获得的数据证实了以下假设，即不同的阿片受体分别负责脑啡肽的致痫作用（δ受体）和抗癫痫作用（μ受体）。小剂量甲硫氨酸脑啡肽的作用似乎在更大程度上反映了内源性脑啡肽在癫痫发生中的作用。
