Inhibition of dopamine beta-hydroxylase by 4-hydroxypyrazole: ethanol-pyrazole effects on serum dopamine beta-hydroxylase in vivo

J Pharmacol Exp Ther. 1978 Jul;206(1):69-74.

Abstract

Chronic pyrazole treatment caused a 40% decrease in rat serum dopamine beta-hydroxylase (DBH) activity. Ethanol given simultaneously with pyrazole prevented the inhibition. 4-Hydroxypyrazole, the major metabolite of pyrazole, competitively inhibited both rat serum DBH and partially purified bovine adrenal DBH in vitro. In vivo, 4-hydroxypyrazole caused large decreases in rat serum (53-84%) and adrenal (97%) DBH activity but had no effect on brain enzyme. The decrease in rat serum DBH after chronic pyrazole treatment and the pyrazole-induced changes in physiological parameters, such as body weight and temperature, may be due to the formation of 4-hydroxypyrazole.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adrenal Glands / drug effects
  • Adrenal Glands / enzymology
  • Animals
  • Cattle
  • Dopamine beta-Hydroxylase / antagonists & inhibitors*
  • Dopamine beta-Hydroxylase / blood
  • Ethanol / pharmacology*
  • Hydroxylation
  • In Vitro Techniques
  • Male
  • Pyrazoles / antagonists & inhibitors
  • Pyrazoles / pharmacology*
  • Rats

Substances

  • Pyrazoles
  • Ethanol
  • Dopamine beta-Hydroxylase