IN VITRO SCREEN OF INHIBITORS OF RAT BRAIN TYROSINE HYDROXYLASE

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Abstract
Over 600 compounds were tested at 10−4 M concentration as inhibitors of tyrosine hydroxylase activity in crude rat-brain homogenate. Most of the compounds had little or no inhibitory effect and those with strong inhibitory properties were, except for a very few oxidizing and complexing agents, all close structural analogues of tyrosine or of its catechol metabolites. Data obtained in this screen are generally in accord with previous data reported in the literature. For high inhibitory activity in the tyrosine series, side-chain substitution is critical. N-Substitution is particularly undesirable. For high inhibitory activity in the catechol series, the ring hydroxy groups should be 3,4 in relation to a C—C—N side chain. Further ring substitution is undesirable, but some side-chain substitution is permissible.