Pharmacological modulation of central monoaminergic systems and influence on the anticonvulsant effectiveness of standard antiepileptics in maximal electroshock seizure.

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.