Vitamin 86 Antagonists
Desoxypyridoxine (2, 4-dimethyl-3-hydroxy-5-hydroxymethylpyridine) has a potent B6 antagonistic action. Its use in animal diets is of value in accentuating B6 deficiency symptoms and decreasing the time required to develop them. The compound is a strong tyrosine decarboxylase inhibitor, for example, but only in the phosphorylated form. Methoxypyridoxine is another antagonist that has been studied in detail. ToxopyrimidiI}e (2-methyl-4-amino-5hydroxymethyl pyrimidine) administration lowers the B6 levels of rat tissues and produces liver damage.
Glutamic acid decarboxylase is inhibited by toxopyrimidine, and the product oftl:1e reaction of this enzyme, y-aminobutyric acid, is lowered in brain tissue ofrats just prior to convulsions. Injection of p-hydroxy-y-aminobutyric acid, but not of y-aminobutyric acid, suppressed the convulsions resulting from toxopyrimidine. The compound isonicotinic acid hrydrazide (INH) in combination with other drugs has been used successfully in the treatment of tuberculosis. Daily doses of 300 to 900 mg caused increased excretion of kynurenine and xanthurenic aeid in tryptophan load tests, according to Price and co-workers. The structure of this drug is given with those ofB6 and r~lated compounds. It is chemically similar to pyridoxine and was thought to opeiate as a-vitamin antagonist.
It is known now that it reacts with pyridoxal forming a hydrazone (aldehyde hydrazone) combining the aldehyde form of the vitamin, RCHO, and the free amino group of the hydrazine, forming RCH=N-NHR', the hydrazone, which is excreted. Heilbron considers that such a reaction cannot be the only mechanism involved in this B6 enzyme, inhibition.
