Endozepines in recurrent stupor

Pietro Cortelli, Rossella Avallone, Mario Baraldi, Maria Luisa Zeneroli, Jessica Mandrioli, Lorenzo Corsi, Roberto Riva, Paolo Tinuper, Elio Lugaresi, Agostino Baruzzi, Pasquale Montagna

Research output: Contribution to journalArticlepeer-review


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 GABAA 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.

Original languageEnglish
Pages (from-to)477-487
Number of pages11
JournalSleep Medicine Reviews
Issue number6
Publication statusPublished - Dec 2005


  • Benzodiazepines
  • Endozepines
  • Hepatic encephalopathy
  • Idiopathic recurrent stupor

ASJC Scopus subject areas

  • Clinical Neurology
  • Dentistry(all)
  • Ophthalmology
  • Pulmonary and Respiratory Medicine
  • Neurology


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