Potent and stereospecific anticonvulsant activity of 3-isobutyl GABA relates to in vitro binding at a novel site labeled by tritiated gabapentin.
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.
Department of Pharmacology, Warner-Lambert Co., Ann Arbor, MI 48105.
C P
CP
Taylor
M G
MG
Vartanian
P W
PW
Yuen
C
C
Bigge
N
N
Suman-Chauhan
D R
DR
Hill
D000085:Acetates / Q000494:pharmacology*; D000588:Amines; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D001667:Binding, Competitive / Q000187:drug effects; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D003509:Cyclohexanecarboxylic Acids; D004597:Electroshock; D000077206:Gabapentin; D007275:Injections, Intravenous; D008297:Male; D051379:Mice; D000069583:Pregabalin; D011963:Receptors, GABA-A / Q000187:drug effects*; D013237:Stereoisomerism; D013570:Synaptic Membranes / Q000187:drug effects / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology
D000085:Acetates; D000588:Amines; D000927:Anticonvulsants; D003509:Cyclohexanecarboxylic Acids; D011963:Receptors, GABA-A; D000069583:Pregabalin; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin