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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 

Pretreatment of CD-1 mice with 4-methylpyrazole blocks toxicity from the gamma-hydroxybutyrate precursor, 1,4-butanediol.

1,4-Butanediol (1,4-BD) is the dihydroxy precursor of gamma-hydroxybutyrate (GHB), a popular recreational drug that has been banned by the United States Food and Drug Administration (FDA) and controlled as a federal schedule I drug. 1,4-BD is enzymatically converted in vivo to GHB by alcohol dehydrogenase ( ADH), and overdoses can result in coma, severe respiratory depression, bradycardia, hypothermia, seizures, and death. Presently, there is no antidote. We pretreated CD-1 mice with the ADH antagonist, 4-methylpyrazole (4-MP), to determine if blocking ADH can prevent or decrease toxicity from 1,4-BD overdose. Pretreatment with 4-MP increased the Toxic Dose-50 (TD(50)) of 1,4-BD for the righting reflex from 585 mg/kg (95% CI, 484-707 mg/kg) in control mice to 5,550 mg/kg (95% CI, 5,353-5,756 mg/kg) in pretreated mice. Pretreatment with 4-MP also increased the TD(50) of 1,4-BD for the rotarod test from 163 mg/kg (95% CI, 136-196 mg/kg) in control mice to 4,900 mg/kg (95% CI, 4,812-4,989 mg/kg) in pretreated mice. Pretreatment with 4-MP significantly decreased the toxicity of 1,4-BD in CD-1 mice, presumably by inhibiting its ADH biotransformation to GHB. 4-MP warrants further investigation as a potential antidote for this increasingly abused drug.[1]

References

  1. Pretreatment of CD-1 mice with 4-methylpyrazole blocks toxicity from the gamma-hydroxybutyrate precursor, 1,4-butanediol. Quang, L.S., Shannon, M.W., Woolf, A.D., Desai, M.C., Maher, T.J. Life Sci. (2002) [Pubmed]
 
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