title: Endozepines in recurrent stupor.
abstract: Stupor is a condition from which the subject can be aroused only by vigorous stimuli. Most patients with stupor have a diffuse organic cerebral dysfunction. Rarely stupor is recurrent and no specific causes can be found. Patients with idiopathic recurrent stupor were awakened by i.v. administration of an antagonist (flumazenil) of the benzodiazepine recognition site located in the GABA(A) receptor. Since no exogenous benzodiazepines were detected in plasma and cerebrospinal fluid by high performance liquid chromatography, an excess of endogenous benzodiazepine-like compounds (endozepines) was proposed as the cause of stupor. The existence of endozepines, their widespread distribution in the CNS and their involvement in hepatic encephalopathy are established. However, the origin of these compounds, how biosynthesis occurs and the mechanisms and causes through which they alter brain functions are poorly understood. The fact that a number of synthetic benzodiazepines are difficult to detect using conventional techniques and the discovery that some cases of recurrent stupor were caused by fraudulent administration of lorazepam question whether the concept of endozepine recurrent stupor can be sustained. This review summarizes the state of endozepine physiology and pharmacology and the clinical syndromes attributed to their involvement. A diagnostic work-up to define endozepine-induced recurrent stupor is suggested.
authors.affiliation: Department of Neurological Sciences, University of Bologna, Via Ugo Foscolo, 7, 40123 Italy. pietro.cortelli@unibo.it
authors.forename: Pietro
authors.initials: P
authors.lastname: Cortelli
authors.forename: Rossella
authors.initials: R
authors.lastname: Avallone
authors.forename: Mario
authors.initials: M
authors.lastname: Baraldi
authors.forename: Maria Luisa
authors.initials: ML
authors.lastname: Zeneroli
authors.forename: Jessica
authors.initials: J
authors.lastname: Mandrioli
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Corsi
authors.forename: Roberto
authors.initials: R
authors.lastname: Riva
authors.forename: Paolo
authors.initials: P
authors.lastname: Tinuper
authors.forename: Elio
authors.initials: E
authors.lastname: Lugaresi
authors.forename: Agostino
authors.initials: A
authors.lastname: Baruzzi
authors.forename: Pasquale
authors.initials: P
authors.lastname: Montagna
mesh_terms: D003128:Coma / Q000175:diagnosis / Q000188:drug therapy / Q000378:metabolism*; D026261:Diazepam Binding Inhibitor / Q000378:metabolism* / Q000494:pharmacology; D004569:Electroencephalography / Q000706:statistics & numerical data; D005442:Flumazenil / Q000494:pharmacology / Q000627:therapeutic use; D006501:Hepatic Encephalopathy / Q000378:metabolism; D006801:Humans; D011963:Receptors, GABA-A / Q000187:drug effects / Q000502:physiology; D012008:Recurrence
chemical_list: D026261:Diazepam Binding Inhibitor; D011963:Receptors, GABA-A; D005442:Flumazenil