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-fluorobenzylamino)-phenyl) carbamic acid ethyl ester) was evaluated in the amygdala kindling model of complex partial seizures in rats. D-23129 exerts potent anticonvulsant activity against both focal and generalized seizures in animal models of epilepsy. After intraperitoneal and oral administration in kindled rats, the substance dose dependently increased the threshold for induction of afterdischarges, exerting significant effects already after 0.01 mg/kg. In higher doses (2.5-5 mg/kg i.p., 10-15 mg/kg p.o.) D-23129 also exerted anticonvulsant effects on other seizure parameters of amygdala-kindled rats, i.e. seizure severity, seizure duration, total duration of behavioural changes and afterdischarge duration. The adverse effects of D-23129 were quantitated in the open field and in the rotarod test, a standard test for motor impairment. D-23129 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 partial seizures than in other seizure models. D-23129 is orally active and is devoid of neurotoxic effects in anticonvulsant doses, thus indicating that this compound has potential for antiepileptic therapy.
Tober
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C
Department of Pharmacology, ASTA Medica Group, Arzneimittelwerk Dresden, Radebeul, Germany.
Rostock
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A
Rundfeldt
C
C
Bartsch
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R
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology* / Q000633:toxicity; D002219:Carbamates / Q000494:pharmacology*; D005260:Female; D007696:Kindling, Neurologic / Q000187:drug effects*; D010655:Phenylenediamines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012640:Seizures / Q000188:drug therapy*; D014635:Valproic Acid / Q000494:pharmacology
D000927:Anticonvulsants; D002219:Carbamates; D010655:Phenylenediamines; C101866:ezogabine; D014635:Valproic Acid