D-23129 - A POTENT ANTICONVULSANT IN THE AMYGDALA KINDLING MODEL OF COMPLEX PARTIAL SEIZURES

The novel anticonvulsant drug D-23129 (N-(2-amino-4-(4-fluorobenzylami no)-phenyl) carbamic acid ethyl ester) was evaluated in the amygdala k indling model of complex partial seizures in rats. D-23129 exerts pote nt anticonvulsant activity against both focal and generalized seizures in animal models of epilepsy. After intraperitoneal and oral administ ration in kindled rats, the substance dose dependently increased the t hreshold for induction of afterdischarges, exerting significant effect s already after 0.01 mg/kg. In higher doses (2.5-5 mg/kg i.p., 10-15 m g/kg p.o.) D-23129 also exerted anticonvulsant effects on other seizur e parameters of amygdala-kindled rats, i.e. seizure severity, seizure duration, total duration of behavioural changes and afterdischarge dur ation. The adverse effects of D-23129 were quantitated in the open fie ld and in the rotarod test, a standard test for motor impairment. D-23 129 exerted no adverse effects on behaviour in doses up to 5 mg/kg i.p . and 15 mg/kg p.o. Comparing the adverse effects between kindled and non-kindled rats, no differences were found. The data demonstrate that D-23129 is more potent in the amygdala kindling model of complex part ial seizures than in other seizure models. D-23129 is orally active an d is devoid of neurotoxic effects in anticonvulsant doses, thus indica ting that this compound has potential for antiepileptic therapy.