INHALATION ANESTHETIC COMPETITION AT HIGH-AFFINITY COCAINE BINDING-SITES IN RAT-BRAIN SYNAPTOSOMES

We have shown anaesthetics inhibit synaptosomes. In order to determine if this inhibition is associated with occupancy of the cocaine site, we examined binding of [H-3](2 beta-carbomethoxy-3 beta-(4-fluoropheny l)-tropane) (H-3- CFT) in the presence of halothane or isoflurane 0.01 -5 mmol litre(-1) in rat brain synaptosomes. Both anaesthetics inhibit ed H-3-CFT binding (mean K-i 0.61 (SEM 0.12) and 0.75 (0.21) mmol litr e(-1), respectively), by increasing K-d (13.8 (0.6) and 29.8 (12.8) nm ol litre(-1), respectively) compared with control (8.02 (0.5) nmol lit re(-1)) (P < 0.01). Halothane did not change Bmax, but isoflurane incr eased it significantly. Cocaine protected CFT sites from N-ethylmaleim ide alkylation, but neither anaesthetic did. Photoaffinity labelling w ith halothane significantly inhibited H-3-CFT binding compared with UV -exposed controls. We conclude that clinically relevant concentrations of both anaesthetics inhibit high-affinity CFT binding, and the data suggest overlapping sites for halothane and CFT.