Effect of pyrazole, 4-methylpyrazole, 4-bromopyrazole and 4-iodopyrazole on brain noradrenaline levels of mice and rats

Four daily doses of pyrazole (50 mg/kg), caused a reduction in rat brain noradrenaline (NA) of over 20% when determined 24 hrs 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 hrs 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 behaviour. 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 of exploratory behaviour. It is concluded that 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.