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Related Experiment Videos

4-Methylpyrazole alters phenobarbitone hypnotic concentrations in rats.

I Ramzan1

  • 1Department of Pharmaceutical Sciences, University of Pittsburgh School of Pharmacy, PA 15261.

The Journal of Pharmacy and Pharmacology
|November 1, 1988
PubMed
Summary

The liver alcohol dehydrogenase inhibitor, 4-methylpyrazole, enhances central nervous system sensitivity to phenobarbitone in rats. This pretreatment reduces phenobarbitone dose and serum concentrations needed for hypnotic effects.

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Area of Science:

  • Pharmacology
  • Neuroscience

Background:

  • 4-methylpyrazole is a known inhibitor of liver alcohol dehydrogenase.
  • Phenobarbitone is a barbiturate used for its hypnotic and sedative effects.

Purpose of the Study:

  • To investigate the effect of 4-methylpyrazole on the hypnotic concentrations of phenobarbitone in rats.
  • To determine if 4-methylpyrazole alters central nervous system sensitivity to phenobarbitone.

Main Methods:

  • Rats were pretreated with a single intravenous dose of 4-methylpyrazole (1 mmol kg-1) or saline 60 minutes before phenobarbitone administration.
  • Hypnotic effects (loss of righting reflex) and phenobarbitone concentrations in serum, brain, and cerebrospinal fluid were measured.

Main Results:

  • 4-methylpyrazole pretreatment shortened the onset time of phenobarbitone-induced hypnosis.

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  • The dose of phenobarbitone required for hypnosis was reduced by approximately half in 4-methylpyrazole-treated rats.
  • Phenobarbitone concentrations in serum, brain, and cerebrospinal fluid at the onset of hypnosis were also reduced by about half.

    • Conclusions:

    • Acute 4-methylpyrazole pretreatment increases central nervous system sensitivity to phenobarbitone in rats.
    • This enhanced sensitivity appears to be independent of 4-methylpyrazole's inhibitory effect on liver alcohol dehydrogenase.