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A selective imidazobenzodiazepine antagonist of ethanol in the rat.

Publication ,  Journal Article
Suzdak, PD; Glowa, JR; Crawley, JN; Schwartz, RD; Skolnick, P; Paul, SM
Published in: Science
December 5, 1986

Ethanol, at pharmacologically relevant concentrations of 20 to 100 mM, stimulates gamma-aminobutyric (GABA) receptor-mediated uptake of 36Cl-labeled chlorine into isolated brain vesicles. One drug that acts at GABA-benzodiazepine receptors, the imidazobenzodiazepine Ro15-4513, has been found to be a potent antagonist of ethanol-stimulated 36Cl- uptake into brain vesicles, but it fails to antagonize either pentobarbital- or muscimol-stimulated 36Cl- uptake. Pretreatment of rats with Ro15-4513 blocks the anticonflict activity of low doses of ethanol (but not pentobarbital) as well as the behavioral intoxication observed with higher doses of ethanol. The effects of Ro15-4513 in antagonizing ethanol-stimulated 36Cl- uptake and behavior are completely blocked by benzodiazepine receptor antagonists. However, other benzodiazepine receptor inverse agonists fail to antagonize the actions of ethanol in vitro or in vivo, suggesting a novel interaction of Ro15-4513 with the GABA receptor-coupled chloride ion channel complex. The identification of a selective benzodiazepine antagonist of ethanol-stimulated 36Cl- uptake in vitro that blocks the anxiolytic and intoxicating actions of ethanol suggests that many of the neuropharmacologic actions of ethanol may be mediated via central GABA receptors.

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Published In

Science

DOI

ISSN

0036-8075

Publication Date

December 5, 1986

Volume

234

Issue

4781

Start / End Page

1243 / 1247

Location

United States

Related Subject Headings

  • Synaptosomes
  • Receptors, GABA-A
  • Rats, Inbred Strains
  • Rats
  • Pyrazoles
  • Male
  • General Science & Technology
  • Flumazenil
  • Ethanol
  • Chlorides
 

Citation

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Suzdak, P. D., Glowa, J. R., Crawley, J. N., Schwartz, R. D., Skolnick, P., & Paul, S. M. (1986). A selective imidazobenzodiazepine antagonist of ethanol in the rat. Science, 234(4781), 1243–1247. https://doi.org/10.1126/science.3022383
Suzdak, P. D., J. R. Glowa, J. N. Crawley, R. D. Schwartz, P. Skolnick, and S. M. Paul. “A selective imidazobenzodiazepine antagonist of ethanol in the rat.Science 234, no. 4781 (December 5, 1986): 1243–47. https://doi.org/10.1126/science.3022383.
Suzdak PD, Glowa JR, Crawley JN, Schwartz RD, Skolnick P, Paul SM. A selective imidazobenzodiazepine antagonist of ethanol in the rat. Science. 1986 Dec 5;234(4781):1243–7.
Suzdak, P. D., et al. “A selective imidazobenzodiazepine antagonist of ethanol in the rat.Science, vol. 234, no. 4781, Dec. 1986, pp. 1243–47. Pubmed, doi:10.1126/science.3022383.
Suzdak PD, Glowa JR, Crawley JN, Schwartz RD, Skolnick P, Paul SM. A selective imidazobenzodiazepine antagonist of ethanol in the rat. Science. 1986 Dec 5;234(4781):1243–1247.
Journal cover image

Published In

Science

DOI

ISSN

0036-8075

Publication Date

December 5, 1986

Volume

234

Issue

4781

Start / End Page

1243 / 1247

Location

United States

Related Subject Headings

  • Synaptosomes
  • Receptors, GABA-A
  • Rats, Inbred Strains
  • Rats
  • Pyrazoles
  • Male
  • General Science & Technology
  • Flumazenil
  • Ethanol
  • Chlorides