The benzodiazepines and inosine antagonize caffeine-induced seizures

Paul J. Marangos, Andrea M. Martino, Steven M. Paul, Philip Skolnick

Research output: Contribution to journalArticlepeer-review

97 Scopus citations

Abstract

The induction of generalized tonic-clonic seizures in mice by the methylxanthine stimulant caffeine is described. These seizures are indistinguishable in quality from those induced by pentylenetetrazol (PTZ), and pretreatment with low doses of caffeine potentiates PTZ-induced seizures. Benzodiazepines inhibit caffeine-induced seizures with a rank order potency that parallels their affinities for the central nervous system (CNS) benzodiazepine receptor in vitro. Inosine, a purine that has recently been shown to be a competitive inhibitor of [3H] diazepam binding in vitro, antagonizes caffeine-induced seizures, while 7-methyl-inosine, a purine that lacks receptor binding inhibitory activity, has no effect on seizures. Since the benzodiazepines, inosine, caffeine, and pentylenetetrazol all competitively inhibit [3H] diazepam binding and have marked effects on inducing or antagonizing seizures, further study of this receptor-ligand system may provide additional insights that concern possible biochemical mechanisms of seizures.

Original languageEnglish
Pages (from-to)269-273
Number of pages5
JournalPsychopharmacology
Volume72
Issue number3
DOIs
StatePublished - Mar 1 1981

Keywords

  • Benzodiazepines
  • Caffeine
  • Purines
  • Seizures

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