Anxiolytic 2,3-benzodiazepines, their specific binding to the basal ganglia

Edit J. Horváth, Katalin Horváth, Tamás Hámori, M. Fekete, Sándor Sólyom, M. Palkóvits

Research output: Contribution to journalArticle

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Abstract

Over the past 20 years, several members of the 2,3-benzodiazepine family have been synthesized. Some of these compounds - tofisopam (Grandaxin(®)), girisopam, nerisopam - exert significant anxiolytic and antipsychotic activities. Sites where actions of 2,3-benzodiazepines are mediated differ from those of 1,4-benzodiazepines. Binding of 2,3-benzodiazepines to neuronal cells in the central nervous system shows a unique and specific distribution pattern: their binding sites are located exclusively to the basal ganglia. Chemical lesioning of the striato-pallido-nigral system, surgical transections of the striato-nigral pathway and the activation of c-fos expression in the basal ganglia after application of 2,3-benzodiazepines suggest that these compounds mainly bind to projecting neurons of the striatum. The binding sites are transported from the striatum to the substantia nigra and the entopeduncular nucleus. Recent studies on mechanism of action of 2,3-benzodiazepines indicate their possible role in opioid signal transduction since 2,3-benzodiazepines augment the agonist potency of morphine to induce catalepsy and analgesia, and their action is diminished in morphine tolerant animals. The possible biochemical target of 2,3- benzodiazepines is an alteration in the phosphorylation of protein(s) important in the signal transduction process. Agents affecting emotional responses evoked by endogenous opioids without danger of tolerance and dependence may represent a new therapeutic tool in the treatment of addiction and affective disorders.

Original languageEnglish
Pages (from-to)309-342
Number of pages34
JournalProgress in Neurobiology
Volume60
Issue number4
DOIs
Publication statusPublished - Mar 2000

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Anti-Anxiety Agents
Basal Ganglia
Benzodiazepines
Substantia Nigra
Morphine
Opioid Analgesics
Signal Transduction
Entopeduncular Nucleus
Binding Sites
Catalepsy
Mood Disorders
Analgesia
Antipsychotic Agents
Central Nervous System
Phosphorylation
Neurons
Proteins

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Anxiolytic 2,3-benzodiazepines, their specific binding to the basal ganglia. / Horváth, Edit J.; Horváth, Katalin; Hámori, Tamás; Fekete, M.; Sólyom, Sándor; Palkóvits, M.

In: Progress in Neurobiology, Vol. 60, No. 4, 03.2000, p. 309-342.

Research output: Contribution to journalArticle

Horváth, Edit J. ; Horváth, Katalin ; Hámori, Tamás ; Fekete, M. ; Sólyom, Sándor ; Palkóvits, M. / Anxiolytic 2,3-benzodiazepines, their specific binding to the basal ganglia. In: Progress in Neurobiology. 2000 ; Vol. 60, No. 4. pp. 309-342.
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