CNS depressants accelerate the dissociation of 35S-TBPS binding and GABA enhances their displacing potencies.
The specific binding of 35S-t-butylbicyclophosphorothionate (TBPS) was studied in synaptosomal membranes of rat cerebral cortex. The displacing potencies of eleven CNS depressants and three convulsants were determined in the presence of 1 microM GABA and 10 nM R 5135. GABA enhanced the displacing potencies of depressants of most diverse chemical structures: diaryltriazine (LY 81067), pyrazolopyridine (etazolate), cinnamide, glutarimide, 2,3-benzodiazepine (tofizopam) and alcohol derivatives, barbiturates, (+)etomidate, methaqualone and meprobamate. In contrast, the IC50 values of convulsants (picrotoxinin, pentetrazol and the barbiturate enantiomer S(+) MPPB) were not significantly affected. The depressants accelerated either basal or GABA-augmented dissociation of 35-TBPS mainly by increasing the contribution of its rapid first phase.
Maksay
G
G
Central Research Institute for Chemistry, Hungarian Academy of Sciences, Budapest.
Ticku
M K
MK
D000818:Animals; D001643:Bridged Bicyclo Compounds / Q000378:metabolism*; D019086:Bridged Bicyclo Compounds, Heterocyclic; D001952:Bridged-Ring Compounds / Q000378:metabolism*; D002540:Cerebral Cortex / Q000378:metabolism; D018118:Chloride Channels; D002712:Chlorides / Q000502:physiology; D003292:Convulsants / Q000494:pharmacology; D006993:Hypnotics and Sedatives / Q000494:pharmacology*; D066298:In Vitro Techniques; D008565:Membrane Proteins / Q000502:physiology; D051381:Rats; D011963:Receptors, GABA-A / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D001643:Bridged Bicyclo Compounds; D019086:Bridged Bicyclo Compounds, Heterocyclic; D001952:Bridged-Ring Compounds; D018118:Chloride Channels; D002712:Chlorides; D003292:Convulsants; D006993:Hypnotics and Sedatives; D008565:Membrane Proteins; D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid; C037476:tert-butylbicyclophosphorothionate