RT Journal Article
SR Electronic
T1 Tryptophan Derivatives as Inhibitors of Tyrosine Hydroxylase in Vivo and in Vitro
JF Molecular Pharmacology
JO Mol Pharmacol
FD American Society for Pharmacology and Experimental Therapeutics
SP 445
OP 451
VO 4
IS 5
A1 DELTCHO K. ZHELYASKOV
A1 MORTON LEVITT
A1 SIDNEY UDENFRIEND
YR 1968
UL http://molpharm.aspetjournals.org/content/4/5/445.abstract
AB 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.