Hypothermic and toxic actions of 2-butyne-1, 4-diol and other related diols in the rat.

Abstract

Abstract The effects of 2-butyne-1,4-diol (BYDL) and related congeners on the body temperature of the rat have been determined. BYDL, at doses above 0·4 mmol kg−1 intraperitoneally, produced a significant fall in body temperature which was dose dependent. 2-butene-1,4-diol (BEDL) had no hypothermic action, and butane-1,4-diol (BDL) produced only a moderate fall in temperature (1·9°) which correlated with the time course of the hypnotic effect of the drug. γ-Butyrolac-tone (GBL), γ-hydroxybutyric acid (GHB) and pentobarbitone at hypnotic doses had similar hypothermic actions which correlated with the period of hypnosis. The hypothermia produced by BYDL could not be prevented by pretreatment with scopolamine or by maintaining the rats at high environmental temperature (32°). BYDL was far more toxic than the other diols examined (LD50 = 0·609-0·635 mmol kg−1 compared to BEDL: 3·71-3·74 mmol kg−1 and BDL: 11·87-11·90 mmol kg−1). Pretreatment of rats with pyrazole, an inhibitor of liver alcohol dehydrogenase, prevented the toxic and hypothermic actions of BYDL. From earlier studies with pyrazole and BDL it was concluded that BYDL itself was not active but that it was possibly converted in vivo by liver alcohol dehydrogenase to a toxic metabolite.