Electrophysiological and pharmacological actions of the convulsant benzodiazepine Ro 5-4864

Ben Avi Weissman, Jerry Cott, Daniel Hommer, Steven Paul, Phil Skolnick

Research output: Contribution to journalArticle

49 Scopus citations

Abstract

Ro 5-4864 (4′-chlorodiazepam) elicited convulsions in mice with a CD50 of 23.5 mg/kg (i.p.) and increased the firing rate of substantia nigra zona reticula neurons in a dose dependent fashion (0.5-4 mg/kg i.v.). Diazepam and clonazepam, but not Ro 15-1788, were potent inhibitors of Ro 5-4864 induced convulsions. Ro 15-1788 was also ineffective in reversing Ro 5-4864 induced increases in cell firing of zone reticula neurons. Muscimol potently inhibited the seizures and reversed increases in cell firing elicited by Ro 5-4864. Phenobarbital and pentobarbital inhibited Ro 5-4864 induced convulsions with moderate potencies, while phenytoin and carbamazepine were ineffective at doses of up to 100 mg/kg. These observations suggest that Ro 5-4864 does not elicit its pharmacologic actions through a direct action at a 'brain-type' benzodiazepine receptor. However, both the profile and potency of compounds effective in inhibiting the electrophysiological and pharmacological effects of Ro 5-4864 suggest that this compound may act by perturbation of a component of the GABA-benzodiazepine receptor chloride ionophore complex. These findings do not, however, rule out a direct involvement of the high affinity 'peripheral-type' benzodiazepine receptors found in brain.

Original languageEnglish
Pages (from-to)257-263
Number of pages7
JournalEuropean Journal of Pharmacology
Volume97
Issue number3-4
DOIs
StatePublished - Jan 27 1984
Externally publishedYes

Keywords

  • Benzodiazepine receptor
  • Convulsions
  • Muscimol
  • Ro 5-4864
  • Single unit recording

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