title: Acute barbiturate administration increases benzodiazepine receptor binding in vivo.
abstract: Barbiturates have been reported to augment benzodiazepine receptor affinity in vitro, but their effects in vivo are uncertain. We determined benzodiazepine receptor binding in vivo by specific uptake of [3H]Ro15-1788 after barbiturate administration. Pentobarbital (30 mg/kg) increased receptor binding in cerebral cortex and cerebellum at 30 min after injection, with a peak effect occurring at 1 h after dosage, and a return to control levels at 2 h. Specific binding was increased at 1 h after pentobarbital administration in a dose-dependent fashion (7.5-90 mg/kg). Pentobarbital at doses up to 30 mg/kg failed to alter nonspecific binding, but at doses of 60 mg/kg increases in nonspecific binding were observed. The increases in specific binding observed after barbiturate administration were most likely due to a change in apparent receptor affinity, as determined by administration of varying doses of clonazepam to pentobarbital-treated (30 mg/kg) animals. The order of potency of a series of barbiturates in augmenting benzodiazepine receptor binding in cerebral cortex and cerebellum in vivo was: secobarbital greater than pentobarbital greater than amobarbital greater than phenobarbital greater than barbital. The same relative rank order of potency exists for the anesthetic/hypnotic activity of these barbiturates. These data suggest that barbiturates increase the apparent affinity of benzodiazepine receptors in vivo; unlike their in vitro actions, these alterations can be detected with a receptor antagonist.
authors.affiliation: Division of Clinical Pharmacology, Tufts University School of Medicine, Boston, MA 02111.
authors.forename: L G
authors.initials: LG
authors.lastname: Miller
authors.forename: S I
authors.initials: SI
authors.lastname: Deutsch
authors.forename: D J
authors.initials: DJ
authors.lastname: Greenblatt
authors.forename: S M
authors.initials: SM
authors.lastname: Paul
authors.forename: R I
authors.initials: RI
authors.lastname: Shader
mesh_terms: D000818:Animals; D014151:Anti-Anxiety Agents / Q000378:metabolism; D001463:Barbiturates / Q000494:pharmacology*; D001923:Brain Chemistry / Q000187:drug effects; D002998:Clonazepam / Q000494:pharmacology; D005442:Flumazenil / Q000494:pharmacology; D007274:Injections, Intraperitoneal; D008297:Male; D051379:Mice; D010424:Pentobarbital / Q000494:pharmacology; D011963:Receptors, GABA-A / Q000187:drug effects / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D014151:Anti-Anxiety Agents; D001463:Barbiturates; D011963:Receptors, GABA-A; D005442:Flumazenil; D005680:gamma-Aminobutyric Acid; D002998:Clonazepam; D010424:Pentobarbital