D-23129: a new anticonvulsant with a broad spectrum activity in animal models of epileptic seizures

D-23129: a new anticonvulsant with a broad spectrum activity in animal models of epileptic seizures The anticonvulsant activity of the novel drug D-23129 ( N -(2-amino-4-(4-fluorobenzylamino)phenyl)carbamic acid ethyl ester) was evaluated in animal models of epileptic seizures. D-23129 was active after oral and intraperitoneal administration in rats and mice in a range of anticonvulsant tests at nontoxic doses. The compound was active against electrically induced seizures (MES, ED 50 rat p.o. = 2.87 mg/kg), against seizures induced chemically by pentylenetetrazole (s.c. PTZ, ED 50 mouse p.o. = 13.5 mg/kg), picrotoxin and N -methyl- d -aspartate (NMDA) and in genetic animal model, the DBA/2 mouse. It was not active against seizures induced by bicuculline and strychnine. Motor impairment, evaluated with the rotarod test and by observation in the open field, was minimal at doses showing anticonvulsant activity. D-23129 was very effective in elevating the threshold for electrically and chemically induced seizures. Considering the dose increasing the MES threshold by 50% (TID 50 mouse i.p. = 1.6 mg/kg; TID 50 rat i.p. = 0.72 mg/kg) and the TD 50 obtained in the rotarod test, the protective index of D-23129 is better than that of valproate and phenytoin. During 14 days chronic oral treatment with 15 mg/kg, no development of tolerance was observed. D-23129 thus presents an orally active, safe, broad spectrum anticonvulsant agent, which is structurally unrelated to anticonvulsants currently used. We expect that D-23129 will improve the treatment of refractory seizures in humans. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Epilepsy Research Elsevier

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Publisher
Elsevier
Copyright
Copyright © 1996 Elsevier Ltd
ISSN
0920-1211
DOI
10.1016/0920-1211(95)00101-8
Publisher site
See Article on Publisher Site

Abstract

The anticonvulsant activity of the novel drug D-23129 ( N -(2-amino-4-(4-fluorobenzylamino)phenyl)carbamic acid ethyl ester) was evaluated in animal models of epileptic seizures. D-23129 was active after oral and intraperitoneal administration in rats and mice in a range of anticonvulsant tests at nontoxic doses. The compound was active against electrically induced seizures (MES, ED 50 rat p.o. = 2.87 mg/kg), against seizures induced chemically by pentylenetetrazole (s.c. PTZ, ED 50 mouse p.o. = 13.5 mg/kg), picrotoxin and N -methyl- d -aspartate (NMDA) and in genetic animal model, the DBA/2 mouse. It was not active against seizures induced by bicuculline and strychnine. Motor impairment, evaluated with the rotarod test and by observation in the open field, was minimal at doses showing anticonvulsant activity. D-23129 was very effective in elevating the threshold for electrically and chemically induced seizures. Considering the dose increasing the MES threshold by 50% (TID 50 mouse i.p. = 1.6 mg/kg; TID 50 rat i.p. = 0.72 mg/kg) and the TD 50 obtained in the rotarod test, the protective index of D-23129 is better than that of valproate and phenytoin. During 14 days chronic oral treatment with 15 mg/kg, no development of tolerance was observed. D-23129 thus presents an orally active, safe, broad spectrum anticonvulsant agent, which is structurally unrelated to anticonvulsants currently used. We expect that D-23129 will improve the treatment of refractory seizures in humans.

Journal

Epilepsy ResearchElsevier

Published: Apr 1, 1996

References

  • Anticonvulsant properties of D-20443 in genetically epilepsy-prone rats: prediction of clinical response
    Dailey, J.W.; Cheong, J.H.; Ko, K.H.; Adams-Curtis, L.E.; Jobe, P.C.
  • The effects of anticonvulsant compounds on 4-aminopyridine-induced de novo synthesis of neurotransmitter amino acids in rat hippocampus in vitro
    Kapetanovic, I.M.; Yonekawa, W.D.; Kupferberg, H.J.
  • A neuropharmacological evaluation of felbamate as a novel anticonvulsant
    White, H.S.; Wolf, H.H.; Swinyard, A.; Skeen, G.A.; Sofia, R.D.
  • The effects of anticonvulsant agents on 4-aminopyridine induced epileptiform activity in rat hippocampus in vitro
    Yonekawa, W.D.; Kapetanovic, I.M.; Kupferberg, H.J.

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