[Changes in the ligand affinity of benzodiazepine receptors in the presence of 4,5,6,7-tetrahydroisoxazolo(5,4-c)pyridin-3-ol (THIP)].

4,5,6,7-tetrahydroisoxazolo-(5,4-c-)pyridin-3-ol (THIP) in concentrations of 100-500 microM inhibited 3H-flunitrazepam (3H FNZ) binding to intact membranes at 0 degrees C in 25 mM TRIS-HCl buffer. The inhibition of 3H FNZ binding was due to the decrease in the affinity and Bmax of 3H FNZ binding. The affinity for benzodiazepines (e.g. BZ-receptor agonists) was reduced in the presence of THIP, whereas the affinity for BZ-receptor antagonists was unchanged. The value of THIP-induced shift was dependent on the molarity of TRIS-HCl buffer and the concentration of THIP. The results obtained suggest that THIP-induced shifts have a predictive value in the determination of pharmacological efficacy of BZ-receptor ligands.