Fischer W, Müller M
Department of Medicine, Karl Marx University, Leipzig, GDR.
Biomed Biochim Acta. 1988;47(7):631-45.
The influence of various substances modulating the activity of central noradrenergic, serotonergic or dopaminergic neurotransmission systems on the anticonvulsant effectiveness of phenobarbital (phenytoin, carbamazepine) was investigated in mice using the maximal electroshock seizure test (MES). The results demonstrated that especially the noradrenergic system might play a predominant role in modulating the efficiency of the standard antiepileptics tested. In general, pharmacological stimulation with different sympathomimetic drugs (e.g. methamphetamine, maprotiline, tranylcypromine, yohimbine) increased the anticonvulsant activity significantly. Conversely, pharmacological suppression of the noradrenergic system (e.g. 6-OHDA, phenoxybenzamine) reduced the activity of the antiepileptics. In contrast, some beta-receptor blockers with local anesthetic properties (e.g. propranolol, alprenolol, pindolol) were also able to enhance the protective effect of phenobarbital in higher concentrations. The influence of manipulations of serotonergic mechanisms was not so pronounced. However, substances such as 5-HTP, clomipramine, citalopram, zimelidine, showed also additive anticonvulsive effects. On the other hand, the dopaminergic system seemed to exert no significant influence in this respect. These findings give further support to the view that the noradrenergic system may play a remarkable role via the inhibitory function of noradrenaline in the CNS in suppression of epileptic activity and reveal also interesting aspects for a possible comedication in convulsive disorders.
利用最大电休克惊厥试验（MES），在小鼠中研究了调节中枢去甲肾上腺素能、5-羟色胺能或多巴胺能神经传递系统活性的各种物质对苯巴比妥（苯妥英、卡马西平）抗惊厥效果的影响。结果表明，尤其是去甲肾上腺素能系统可能在调节所测试的标准抗癫痫药的效能中起主要作用。一般来说，用不同的拟交感神经药物（如甲基苯丙胺、马普替林、反苯环丙胺、育亨宾）进行药理刺激可显著提高抗惊厥活性。相反，去甲肾上腺素能系统的药理抑制（如6-羟基多巴胺、酚苄明）会降低抗癫痫药的活性。相比之下，一些具有局部麻醉特性的β受体阻滞剂（如普萘洛尔、阿普洛尔、吲哚洛尔）在较高浓度时也能够增强苯巴比妥的保护作用。5-羟色胺能机制操作的影响并不那么明显。然而，诸如5-羟色氨酸、氯米帕明、西酞普兰、齐美利定等物质也显示出相加的抗惊厥作用。另一方面，多巴胺能系统在这方面似乎没有显著影响。这些发现进一步支持了这样一种观点，即去甲肾上腺素能系统可能通过去甲肾上腺素在中枢神经系统中的抑制功能在抑制癫痫活动中发挥显著作用，并且还揭示了惊厥性疾病联合用药可能的有趣方面。
