PMID: 7336957May 1, 1981Paper

Pharmacological and toxicological properties of 4-hydroxypyrazole, a metabolite of pyrazole

Acta Pharmacologica Et Toxicologica
E MacDonaldJ P Pispa

Abstract

The effects of 4-hydroxypyrazole (4-HP), a principal metabolite of pyrazole, were studied in mice. The compound was toxic, much more so than pyrazole with an LD50 of 1.1 mmol/kg (92 mg/Kg) and doses greater than 1.5 mmol/kg (126 mg/kg) were almost invariably fatal. Toxicity seemed to be centered on the liver with microscopic evidence of centrolobular necrosis apparent. Mouse liver catalase was almost totally inhibited 1 hour after administration of 1 mmol/kg of 4-HP. Tryptophan pyrrolase was also inhibited 4-HP seemed to penetrate into the brain as judged by inhibition of brain catalase activity. A slight increase in brain serotonin concentration was found but 4-HP had no effect in the doses used (1.5 mmol/kg or 4 x 1.0 mmol/kg) in brain or heart noradrenaline. We conclude that the pyrazole-induced decrease in brain noradrenaline is not mediated via 4-HP. Furthermore, simultaneous treatment with methanol and pyrazole, which prevents the formation of 4-HP, did not prevent the decrease in brain noradrenaline levels. Since methanol prevented the pyrazole-induced decrease in brain catalase activity, we can also rule out the possibility that the decrease in brain noradrenaline is secondary to pyrazole-induced inhibition of brain cat...Continue Reading

References

Jun 1, 1978·Neurochemical Research·F C BrownJ S Zawad
Aug 1, 1975·Acta Pharmacologica Et Toxicologica·E MacDonaldU Nousianinen
Apr 15, 1974·Biochemical Pharmacology·E FeytmansF Leighton
Oct 15, 1972·Experientia·G MagnussonE Hansson

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Citations

Jul 10, 2002·Annals of the New York Academy of Sciences·Lawrence S QuangTimothy J Maher
Jul 3, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Yoshihide UsamiHiroki Yoneyama

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