RT Journal Article
SR Electronic
T1 Tryptophan Derivatives as Inhibitors of Tyrosine Hydroxylase <em>in Vivo</em> and <em>in Vitro</em>
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.