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Psychopharmacology

, Volume 102, Issue 2, pp 239–242 | Cite as

Action of chlormethiazole in a model of ethanol withdrawal

  • A. R. Green
  • E. M. Davies
  • H. J. Little
  • M. A. Whittington
  • A. J. Cross
Original Investigations

Abstract

Mice withdrawn from exposure for 14 days to ethanol inhalation showed the expected signs of ethanol withdrawal including convulsive behaviour. Injection of chlormethiazole (100 mg/kg) 5 h after the start of withdrawal, at the time that the convulsive behaviour was near maximal, resulted in the virtual disappearance of the withdrawal — induced behaviour within 30 min, with its reappearance by 60 min. A dose of chlormethiazole of 40 mg/kg was without effect. The time course of the effect of chlormethiazole (100 mg/kg) in the withdrawal test was similar to its effect in raising seizure threshold and decreasing locomotor activity. Chlormethiazole did not alter in vitro binding of [3H]-PN 200-110 to the dihydropyridine sensitive Ca2+ channel. Chlormethiazole, a drug used clinically to treat ethanol withdrawal, has therefore been shown to be effective in this animal model of withdrawal. Dihydropyridine calcium antagonists are also active in the model but chlormethiazole is likely to work by a different mechanism and it is suggested that this may be by increasing GABAergic function.

Key words

Chlormethiazole Alcohol withdrawal Convulsions Locomotor activity Dihydropyridines 

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Copyright information

© Springer-Verlag 1990

Authors and Affiliations

  • A. R. Green
    • 1
  • E. M. Davies
    • 1
  • H. J. Little
    • 2
  • M. A. Whittington
    • 2
  • A. J. Cross
    • 1
  1. 1.Astra Neuroscience Research UnitLondonUK
  2. 2.Department of Pharmacology, The Medical SchoolUniversity WalkBristolUK

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