Potent and stereospecific anticonvulsant activity of 3-isobutyl GABA relates to in vitro binding at a novel site labeled by tritiated gabapentin

C P Taylor; M G Vartanian; P W Yuen; C Bigge; N Suman-Chauhan; D R Hill

doi:10.1016/0920-1211(93)90070-n

Potent and stereospecific anticonvulsant activity of 3-isobutyl GABA relates to in vitro binding at a novel site labeled by tritiated gabapentin

Epilepsy Res. 1993 Jan;14(1):11-5. doi: 10.1016/0920-1211(93)90070-n.

Authors

C P Taylor¹, M G Vartanian, P W Yuen, C Bigge, N Suman-Chauhan, D R Hill

Affiliation

¹ Department of Pharmacology, Warner-Lambert Co., Ann Arbor, MI 48105.

PMID: 8383597
DOI: 10.1016/0920-1211(93)90070-n

Abstract

3-Isobutyl GABA is a derivative of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) and is also structurally related to the novel anticonvulsant gabapentin. The S(+) enantiomer of 3-isobutyl GABA blocks maximal electroshock seizures in mice and also potently displaces tritiated gabapentin from a novel high-affinity binding site in rat brain membrane fractions. The R(-) enantiomer is much less active in both assays, suggesting that the gabapentin binding site is involved in the anticonvulsant activity of 3-isobutyl GABA.

MeSH terms

Acetates / pharmacology*
Amines*
Animals
Anticonvulsants / pharmacology*
Binding, Competitive / drug effects
Cerebral Cortex / drug effects
Cerebral Cortex / metabolism
Cyclohexanecarboxylic Acids*
Electroshock
Gabapentin
Injections, Intravenous
Male
Mice
Pregabalin
Receptors, GABA-A / drug effects*
Stereoisomerism
Synaptic Membranes / drug effects
Synaptic Membranes / metabolism
gamma-Aminobutyric Acid / analogs & derivatives*
gamma-Aminobutyric Acid / metabolism
gamma-Aminobutyric Acid / pharmacology

Substances

Acetates
Amines
Anticonvulsants
Cyclohexanecarboxylic Acids
Receptors, GABA-A
Pregabalin
gamma-Aminobutyric Acid
Gabapentin