Inhibition of neuronal membrane GABAB receptor binding by GABA structural analogues.
1. A number of compounds structurally related to GABA were tested as inhibitors of baclofen-sensitive GABAB receptor binding to membranes from mouse brain. 2. In addition to two known inhibitors--baclofen and 5-aminovaleric acid--two analogues were shown to possess inhibitory activity. These compounds were 4-aminobutyryl-DL-alanine hydrobromide (IC50 = 3 microM) and trans-2-(aminomethyl)cyclopropane carboxylic acid (IC50 = 90 microM). 3. Both drugs also exhibited affinity for GABAA binding sites. 4. Further experiments are needed to establish if these analogues exert agonist or antagonist action at the GABAB receptor.
Tunnicliff
G
G
Laboratory of Neurochemistry, Indiana University School of Medicine, Evansville 47712.
Rogier
C J
CJ
Youngs
T L
TL
D000612:4-Aminobutyrate Transaminase / Q000378:metabolism; D000409:Alanine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000596:Amino Acids / Q000494:pharmacology; D000598:Amino Acids, Cyclic; D021542:Amino Acids, Neutral; D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D001667:Binding, Competitive; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009474:Neurons / Q000378:metabolism*; D011963:Receptors, GABA-A / Q000187:drug effects / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology
D000596:Amino Acids; D000598:Amino Acids, Cyclic; D021542:Amino Acids, Neutral; D011963:Receptors, GABA-A; C055417:4-aminobutylalanine; C023410:2-(aminomethyl)cyclopropanecarboxylic acid; D005680:gamma-Aminobutyric Acid; C013809:5-aminovaleric acid; D000612:4-Aminobutyrate Transaminase; D001418:Baclofen; D000409:Alanine