title: Flumazenil provocation of panic attacks. Evidence for altered benzodiazepine receptor sensitivity in panic disorder.
abstract: The possibility that panic disorder might be due to abnormal activity of endogenous ligands of the benzodiazepine receptor was investigated with the use of the benzodiazepine antagonist flumazenil. Physiological and subjective psychological responses to this selective antagonist were measured in 10 patients with panic disorder and in 10 control subjects, by using a placebo-controlled crossover study design. Subjective anxiety responses after flumazenil infusion were significantly higher in the patient group with panic disorder than in the controls, and eight patients with panic disorder but no controls had panic attacks. This anxiogenic effect of flumazenil in the patients argues against the presence of endogenous anxiogenic (inverse agonist) ligands. Possible explanations include the differential production of an anxiolytic endogenous ligand or an altered benzodiazepine receptor "set-point." Such an abnormality may contribute to the pathogenesis of panic disorder.
authors.affiliation: Reckitt & Colman Psychopharmacology Unit, School of Medical Sciences, Bristol, United Kingdom.
authors.forename: D J
authors.initials: DJ
authors.lastname: Nutt
authors.forename: P
authors.initials: P
authors.lastname: Glue
authors.forename: C
authors.initials: C
authors.lastname: Lawson
authors.forename: S
authors.initials: S
authors.lastname: Wilson
mesh_terms: D000293:Adolescent; D000328:Adult; D001008:Anxiety Disorders / Q000139:chemically induced* / Q000503:physiopathology / Q000523:psychology; D001794:Blood Pressure / Q000187:drug effects; D004311:Double-Blind Method; D005260:Female; D005442:Flumazenil / Q000008:administration & dosage / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007262:Infusions, Intravenous; D008024:Ligands; D008297:Male; D010200:Panic; D010919:Placebos; D011963:Receptors, GABA-A / Q000187:drug effects* / Q000502:physiology
chemical_list: D008024:Ligands; D010919:Placebos; D011963:Receptors, GABA-A; D005442:Flumazenil