Diazepam enhances the action but not the binding of the GABA analog, THIP.
GABA (4-aminobutyric acid) and its bicyclic analog THIP (4,5,6,7-tetrahydroisoxazolo-[4,5-c]-pyridin-3-ol) produced membrane hyperpolarization and increased chloride ion conductance of mouse spinal cord neurons in cell culture. Above 1 nM diazepam enhanced the actions of both GABA and THIP with similar potency and efficacy. Diazepam has been shown to enhance the binding of [3H]GABA to rat brain membranes over similar concentration ranges, with the EC50 values for enhancement of [3H]GABA binding and increase in membrane conductance being similar. In contrast, binding of [3H]THIP has been shown to be unaltered by diazepam under a variety of conditions. The possible reasons for such a discrepancy between these electrophysiological and neurochemical results with THIP are discussed.
D000818:Animals; D001921:Brain / Q000378:metabolism; D002712:Chlorides / Q000378:metabolism; D046508:Culture Techniques; D003975:Diazepam / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005727:Ganglia, Spinal / Q000187:drug effects; D007555:Isoxazoles / Q000008:administration & dosage* / Q000378:metabolism; D008564:Membrane Potentials; D051379:Mice; D010080:Oxazoles / Q000008:administration & dosage*; D051381:Rats; D013116:Spinal Cord / Q000187:drug effects
D002712:Chlorides; D007555:Isoxazoles; D010080:Oxazoles; C015542:gaboxadol; D003975:Diazepam