PMID- 2714371 OWN - NLM STAT- MEDLINE DCOM- 19890615 LR - 20190624 IS - 0014-2999 (Print) IS - 0014-2999 (Linking) VI - 172 IP - 1 DP - 1989 Mar 7 TI - Acute inactivation of tryptophan hydroxylase by amphetamine analogs involves the oxidation of sulfhydryl sites. PG - 93-7 AB - The activity of rat hippocampal tryptophan hydroxylase was reduced from 30-60% 3 h after the administration of a 10-15 mg/kg dose of either fenfluramine, methamphetamine or 3,4-methylenedioxymethamphetamine (MDMA). Tryptophan hydroxylase inactivated by these drug treatments could be reconstituted by a prolonged anaerobic incubation in the presence of 5 mM dithiothreitol and 50 microM Fe2+. Drug-inactivated enzyme obtained from rats killed 18 h after multiple doses of either D(+)- or L(-)-MDMA could not be similarly restored. These observations suggest that the rapid decrease in central tryptophan hydroxylase activity induced by amphetamine analogs results from the reversible oxidation of a sulfhydryl site(s) within the enzyme molecule, whereas the irreversible decrease in enzymatic activity measured 18 h after multiple-dose MDMA treatment may reflect serotonergic toxicity. FAU - Stone, D M AU - Stone DM AD - Department of Pharmacology and Toxicology, University of Utah, Salt Lake City 84112. FAU - Johnson, M AU - Johnson M FAU - Hanson, G R AU - Hanson GR FAU - Gibb, J W AU - Gibb JW LA - eng GR - DA 00869/DA/NIDA NIH HHS/United States GR - DA 04221/DA/NIDA NIH HHS/United States PT - Journal Article PT - Research Support, U.S. Gov't, P.H.S. PL - Netherlands TA - Eur J Pharmacol JT - European journal of pharmacology JID - 1254354 RN - 0 (Amphetamines) RN - 0 (Sulfhydryl Compounds) RN - E1UOL152H7 (Iron) RN - EC 1.14.16.4 (Tryptophan Hydroxylase) RN - T8ID5YZU6Y (Dithiothreitol) SB - IM MH - Amphetamines/*pharmacology MH - Anaerobiosis MH - Animals MH - Dithiothreitol/pharmacology MH - Enzyme Activation/drug effects MH - Hippocampus/enzymology MH - Iron/pharmacology MH - Male MH - Oxidation-Reduction MH - Rats MH - Rats, Inbred Strains MH - Sulfhydryl Compounds/*analysis MH - Tryptophan Hydroxylase/*antagonists & inhibitors EDAT- 1989/03/07 00:00 MHDA- 1989/03/07 00:01 CRDT- 1989/03/07 00:00 PHST- 1989/03/07 00:00 [pubmed] PHST- 1989/03/07 00:01 [medline] PHST- 1989/03/07 00:00 [entrez] AID - 10.1016/0922-4106(89)90048-5 [doi] PST - ppublish SO - Eur J Pharmacol. 1989 Mar 7;172(1):93-7. doi: 10.1016/0922-4106(89)90048-5.