Abstract

Certain typtophan analogs were found to be potent inhibitors of tyrosine hydroxylase and to act by a mechanism that is not competitive with substrate. The most active compounds in these studies were those with a hydroxyl group at the 5 position on the indole ring. The most potent inhibitor was α-methyl-5-hydroxytryptophan. Amines or acids resulting from metabolism of the parent compounds were found to be inactive. Tyrosine hydroxylase activity was inhibited in vivo after a 50 mg/kg dose of α-methyl-5-hydroxytryptophan; a single dose of 200 mg/kg inhibited the enzyme up to 48 hr. Administration of this compound resulted in depletion of tissue stores of catecholamines as well as in sedation.