Propofol potentiates the binding of [3H]flunitrazepam to the GABAA receptor complex.
Propofol (2,6-diisopropylphenol) robustly stimulated the binding of 1 nM [3H]flunitrazepam (FNZ) to rat brain membranes with an EC50 of 146 microM in chloride-free buffer and 23 microM 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 GABAA-benzodiazepine receptor was closely correlated with their permeabilities at this ion channel. Propofol, at a concentration of 300 microM, 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 microM, 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 [3H]flunitrazepam binding.
Prince
R J
RJ
Department of Pharmacology, School of Pharmacy, London, UK.
Simmonds
M A
MA
D000818:Animals; D001667:Binding, Competitive; D004357:Drug Synergism; D005445:Flunitrazepam / Q000378:metabolism*; D008297:Male; D010424:Pentobarbital / Q000494:pharmacology; D011277:Pregnanediones / Q000494:pharmacology; D015742:Propofol / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000378:metabolism*; D014316:Tritium
D011277:Pregnanediones; D011963:Receptors, GABA-A; D014316:Tritium; D005445:Flunitrazepam; C006477:alphaxalone; D010424:Pentobarbital; D015742:Propofol