Anticonvulsant properties of the GABA receptor agonist, progabide, in the kindled amygdaloid seizure model of epilepsy

R. M. Joy, Timothy E Albertson, L. G. Stark

Research output: Contribution to journalArticle

Abstract

Progabide (SL 76002, 4-[(4-chlorophenyl)(5-fluoro-2-hydroxyphenyl)-methylene]amino butanamide) is a GABA receptor agonist which readily enters the brain. Progabide exhibits a broad spectrum of anticonvulsant activity against a number of seizure models, some of which involve GABA mechanisms and some of which do not. We report here that progabide is also anticonvulsant in the kindled amygdaloid seizure (KAS) model of epilepsy in rats. In previously kindled rats progabide, administered ip 30 minutes before testing, reduced afterdischarge (AD) duration and seizure severity. The ED50 for reducing AD duration was approximately 400 mg/kg, a dose also producing some sedation and ataxia. Daily dosing with 100 or 200 mg/kg progabide, ip, 30 minutes before stimulation retarded the acquisition of KAS. Kindling took 7.0 ± 1.0 days in control subjects and 10.5 ± 1.0 or 14.8 ± 0.7 days in the low and high dose groups, respectively. The total AD taken by the groups to reach the fully kindled condition was not modified by progabide. These results suggest that stimulation of GABA systems results primarily in a reduction of AD duration and seizure severity. It dose not seem to significantly modify the evolution of the kindling process, per se.

Original languageEnglish (US)
JournalFederation Proceedings
Volume42
Issue number3
StatePublished - 1983

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GABA Agonists
Anticonvulsants
Epilepsy
Seizures
gamma-Aminobutyric Acid
progabide
Ataxia
Brain

ASJC Scopus subject areas

  • Medicine(all)

Cite this

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abstract = "Progabide (SL 76002, 4-[(4-chlorophenyl)(5-fluoro-2-hydroxyphenyl)-methylene]amino butanamide) is a GABA receptor agonist which readily enters the brain. Progabide exhibits a broad spectrum of anticonvulsant activity against a number of seizure models, some of which involve GABA mechanisms and some of which do not. We report here that progabide is also anticonvulsant in the kindled amygdaloid seizure (KAS) model of epilepsy in rats. In previously kindled rats progabide, administered ip 30 minutes before testing, reduced afterdischarge (AD) duration and seizure severity. The ED50 for reducing AD duration was approximately 400 mg/kg, a dose also producing some sedation and ataxia. Daily dosing with 100 or 200 mg/kg progabide, ip, 30 minutes before stimulation retarded the acquisition of KAS. Kindling took 7.0 ± 1.0 days in control subjects and 10.5 ± 1.0 or 14.8 ± 0.7 days in the low and high dose groups, respectively. The total AD taken by the groups to reach the fully kindled condition was not modified by progabide. These results suggest that stimulation of GABA systems results primarily in a reduction of AD duration and seizure severity. It dose not seem to significantly modify the evolution of the kindling process, per se.",
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