Abstract

Studies relating to the inhibition in vitro are reviewed, with some emphasis on inactivation of coenzyme by the substrate and its analogues, and on carbonyl trapping agents, but more specifically on analogues of certain hydroxycinnamic acids which inhibit dopa-, dops- and 5-HTP-decarboxylases. The structural features of such inhibitors are analyzed, as well as their specificity and competitive nature.

The nature and characteristics of dopa decarboxylation in vivo are discussed, particularly as affected by the absence of visceral organs, and by the thyroid hormone, adrenal cortex, sex and vitamin B₆.

A review and analysis is made of the work pointing to changes in apoenzyme and coenzyme caused by hyperthyroidism and vitamin B₆ deficiency.

Chemical and pharmacological evidence is presented which shows that the substances which inhibit dopa decarboxylase in vitro also are generally effective in vivo. Twenty-five in vitro inhibitors and 50 structurally related noninhibitors have been assessed in several hundred animals. This has led to an understanding of the structural requirements for effective inhibition in vivo, which are essentially the same as for inhibition in vitro.

A possible alternate biosynthetic route to noradrenaline and adrenaline may be by transamination of hydroxyphenylpyruvic acids and subsequent decarboxylation of the resulting amino acids, which is blocked by the inhibitors at the decarboxylation step.

The duration of inhibition and the detoxication of the inhibitors have been studied, and various structural modifications and pharmacological procedures have been investigated for prolonging the duration of the inhibition.

One inhibitor was shown to inhibit the biosynthesis of adrenal medullary adrenaline in insulin-treated rats.