Effect oi Pyrazole, 4–Methylpyrazole, 4–Bromopyrazole and 4–Iodopyrazole on Brain Noradrenaline Levels of Mice and Rats

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Abstract
Four daily doses of pyrazole (50 mg/kg) caused a reduction in rat brain noradrenaline (NA) of > 20% when determined 24 h after the final injection. Neither 4-methylpyrazole (10-50 mg/kg), nor 4-iodopyrazole (10-50 mg/kg) had any effect. In mice treated similarly, pyrazole (50-400 mg/kg) caused a dose-dependent decrease in brain NA. Neither 4-methylpyrazole, 4-bromopyrazole nor 4-iodopyrazole caused any significant change in the levels. However if the brain NA levels were examined 6 h after a single dose, then in addition to pyrazole, 4-methylpyrazole showed a dose-dependent ability to lower brain NA. 4-Bromopyrazole and 4-iodopyrazole, given acutely, caused a dose-dependent decrease in rectal temperature and exploratory behavior. 4-Methylpyrazole, in high doses (200-400 mg/kg) showed similar properties but they did not correlate with the decrease in brain NA. Pyrazole, after acute treatment, showed little ability to change rectal temperature or exploratory behavior. The NA-depleting effect of pyrazole is not related to inhibition of alcohol dehydrogenase, since other 4-substituted pyrazoles which are more potent inhibitors of the enzyme have little or no effect on brain NA levels. [Pyrazole interferes with ethanol metabolism and has been proposed for use in the treatment of ethylene glycol poisoning.].