Enhancement of the in vivo binding of [3H]flunitrazepam by the atypical neuroleptic, clozapine.
Modulation of the benzodiazepine receptor/GABA receptor/chloride ionophore complex in vivo involves a number of intricate regulatory interactions between the three components of the receptor complex. One way to assess these potential interactions involves the in vivo labelling of the benzodiazepine receptor with [3H]flunitrazepam. In these studies, we used this approach to demonstrate that the neuroleptic, clozapine, increases [3H]flunitrazepam binding in mouse brain in a bicuculline-reversible manner. This potentiation of benzodiazepine binding was not antagonized by picrotoxin and was found to result from a slower dissociation of [3H]flunitrazepam from the benzodiazepine receptor. These data suggest that clozapine acts to increase [3H]flunitrazepam binding via a GABAergic mechanism, independent of the chloride channel.
D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D003024:Clozapine / Q000494:pharmacology*; D003984:Dibenzazepines / Q000494:pharmacology*; D004347:Drug Interactions; D005445:Flunitrazepam / Q000378:metabolism*; D008297:Male; D051379:Mice; D009118:Muscimol / Q000494:pharmacology; D011963:Receptors, GABA-A / Q000187:drug effects / Q000502:physiology
D003984:Dibenzazepines; D011963:Receptors, GABA-A; D009118:Muscimol; D005445:Flunitrazepam; D003024:Clozapine; D001640:Bicuculline