Studies of pyridoxine displacement.

Relatively little work has been done with pyridoxine displacers. Ott (1) found 2,4-dimethyl-3-hydroxy-5-hydroxymethylpyridoxine (desoxypyridoxine) to be a very potent inhibitor of pyridoxine in the metabolism of the chick. 2 molecules of inhibitor were sufficient to offset the vitamin activity of 1 molecule of pyridoxine. In the course of an investigation of antimalarials, McCasland et al. (2) synthesized Z-methyl4-hydroxy-6-hydroxymethylpyrimidine and a number of closely related compounds which are analogues of pyridoxine. No statement was made of their activity. The second paper by this group (3), reports the synthesis of 2, B-di-(hydroxymethyl)-4-hydroxy-5-methylpyrimidine hydrochloride which is the pyrimidine analogue of pyridoxine. Tests for antipyridoxine activity of this compound showed it to be inactive. Ott1 found 2-methyl-3-hydroxy-4-methoxymethyl-5-hydroxymethylpyridine (methoxypyridoxine) to be nearly as effective a pyridoxine displacer in the chick as was desoxypyridoxine. Mushett et al. (4) have reported on the pathologic effects produced by these two analogues of pyridoxine. Atrophy of the lymphoid tissues seemed to characterize the histopathological picture. The effectiveness of desoxypyridoxine in the rat has been reported (5). The Merck group (6) has studied the effect of pyridoxinedisplacing agents on the metabolism of tryptophan. From this study, it was concluded that desoxypyridoxine interfered with some phase of tryptophan metabolism. Recently, Beiler and Martin (7) found desoxypyridoxine to be ineffective as an inhibitor of the action of tyrosine decarboxylase. Phosphorylated desoxypyridoxine, on the other hand, displaces pyridoxal phosphate in the tyrosine decarboxylase system.