PROPOFOL POTENTIATES THE BINDING OF [H-3] FLUNITRAZEPAM TO THE GABA-A RECEPTOR COMPLEX

Propofol (2,6-diisopropylphenol) robustly stimulated the binding of 1 nM [H-3]flunitrazepam (FNZ) to rat brain membranes with an EC50 of 146 muM in chloride-free buffer and 23 muM in buffer containing 200 mM NaCl. NaCl showed an EC50 of 40 mM for its ability to increase the potency of propofol. The ability of a range of anions to potentiate propofol's interactions with the GABA(A)-benzodiazepine receptor was closely correlated with their permeabilities at this ion channel. Propofol, at a concentration of 300 muM, decreased the EC50 for the potentiation of FNZ binding by NaCl from 39 mM to 13 mM, with no change in the maximal potentiation. At a concentration of 30 muM, propofol significantly decreased the EC50 for potentiation of FNZ binding by the neurosteroid alphaxalone whilst increasing that for potentiation by pentobarbitone. We conclude that propofol is a potent barbiturate-like modulator of [H-3]flunitrazepam binding.