PYRAZOLO- AND TRIAZOLOPYRIMIDINES AS INHIBITORS OF TRYPTOPHAN PYRROLASE

In a previous paper (1) we reported that allopurinol [4-hydroxy-pyrazolo-(3,4-d)pyrimidine], when administered to rats and mice at dose levels employed in the treatment of gout (2), was a potent inhibitor of tryptophan pyrrolase (TP). Kinetic studies on the enzyme in vitro indicated that the inhibition was noncompetitive (1). Green and Curzon (3) have recently shown that allopurinol, while it does not block hydrocortisone induction of TP, does inhibit the enzymatic activity of formed pyrrolase thus preventing the concomitant decrease in brain 5-hydroxytryptamine levels. The in vitro inhibition of TP by allopurinol has been confirmed by Chytil (4), who has concluded that the effect of allopurinol on TP is contigent upon its inhibition of xanthine oxidase. The results presented in the present paper indicate essentially that no direct relationship exists between the inhibition of xanthine oxidase and TP by various purine analogues related to allopurinol, thus not supporting the mechanism of action proposed by Chytil (4). © 1969.