Single application of a CB1 receptor antagonist rapidly following head injury prevents long-term hyperexcitability in a rat model

Epilepsy Res. 2009 Jul;85(1):123-7. doi: 10.1016/j.eplepsyres.2009.02.019. Epub 2009 Apr 15.

Abstract

Effective prophylaxis for post-traumatic epilepsy currently does not exist, and clinical trials using anticonvulsant drugs have yielded no long-term antiepileptogenic effects. We report that a single, rapid post-traumatic application of the proconvulsant cannabinoid type-1 (CB1) receptor antagonist SR141716A (Rimonabant-Acomplia) abolishes the long-term increase in seizure susceptibility caused by head injury in rats. These results indicate that, paradoxically, a seizure-enhancing drug may disrupt the epileptogenic process if applied within a short therapeutic time window.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Anticonvulsants / therapeutic use
  • Craniocerebral Trauma / complications
  • Craniocerebral Trauma / drug therapy*
  • Disease Models, Animal
  • Electroencephalography / methods
  • Epilepsy, Post-Traumatic / etiology
  • Epilepsy, Post-Traumatic / prevention & control*
  • Pentobarbital / therapeutic use
  • Piperidines / therapeutic use*
  • Pyrazoles / therapeutic use*
  • Rats
  • Rats, Wistar
  • Receptor, Cannabinoid, CB1 / antagonists & inhibitors*
  • Rimonabant

Substances

  • Anticonvulsants
  • Piperidines
  • Pyrazoles
  • Receptor, Cannabinoid, CB1
  • Pentobarbital
  • Rimonabant