Benzodiazepine receptor affinity alterations at physiologic temperature after chronic clonazepam exposure.
Cerebral cortical cell cultures obtained from fetal mice were exposed to 200 nM clonazepam (CZP) for 14 days and benzodiazepine (BDZ) receptor binding was measured on intact cells in situ at 37 degrees C. Total, specific, and CZP-displaceable BDZ binding were significantly reduced from control values immediately after drug removal (77.7 +/- 1.4%, 75.1 +/- 3.0%, and 40.9 +/- 6.0% of control, respectively) but Ro5-4864-displaceable binding was not affected (87.6 +/- 5.1%). Binding returned to control values within 48 hours. Saturation analysis of the binding data indicated that a high-affinity binding site could not be detected in CZP-exposed cultures immediately after drug removal (162 nM versus 49 nM in controls, p less than .001), but was present 24 hours later.
D000818:Animals; D001570:Benzodiazepinones / Q000494:pharmacology; D001831:Body Temperature; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D002998:Clonazepam / Q000378:metabolism / Q000494:pharmacology*; D003292:Convulsants / Q000494:pharmacology; D005445:Flunitrazepam / Q000378:metabolism; D007700:Kinetics; D051379:Mice; D011963:Receptors, GABA-A / Q000187:drug effects / Q000378:metabolism*; D013997:Time Factors
D001570:Benzodiazepinones; D003292:Convulsants; D011963:Receptors, GABA-A; C028513:4'-chlorodiazepam; D002998:Clonazepam; D005445:Flunitrazepam