Short-term effects of 2,4,5-trihydroxyamphetamine, 2,4,5-trihydroxymethamphetamine and 3,4-dihydroxymethamphetamine on central tryptophan hydroxylase activity

J Pharmacol Exp Ther. 1993 May;265(2):813-8.


In previous studies, we have reported the long-term effects of several metabolites of 3,4-methylenedioxymethamphetamine (MDMA) on tryptophan hydroxylase (TPH) activity. In this study, the short-term effects of three metabolites of MDMA. 2,4,5-trihydroxyamphetamine (THA), 2,4,5-trihydroxymethamphetamine (THM) and 3,4-dihydroxymethamphetamine, and the in vitro effect of THA on TPH activity are reported. After short-term treatment, hippocampal TPH activity was decreased to 8 and 54% of control in response to THA and THM, respectively, but was unaltered after 3,4-dihydroxymethamphetamine. Incubating TPH from THM-treated rats with dithiothreitol under nitrogen failed to reverse the decrease in enzyme activity induced by THM treatment. THA also decreased tyrosine hydroxylase activity to 75% of control, whereas the enzyme activity remained unaltered by THM. The structural analog of THA, 6-hydroxydopamine, failed to reproduce the effect of THA on TPH activity; however, 5,6-dihydroxytryptamine decreased hippocampal TPH activity to 18% of control. In the in vitro study, the hippocampus and the striatum were incubated in varying concentrations of THA. After a 1-h incubation at 37 degrees C, hippocampal TPH activity was decreased to 83, 71, 68, 47 and 3% of control after exposure to 0.001, 0.01, 0.1, 0.5 or 5.0 mM THA, respectively; striatal TPH activity was reduced to 98, 95, 70, 54 and 17% of control, respectively. Incubating the enzyme under reducing conditions failed to restore the enzyme activity to control levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 5,6-Dihydroxytryptamine / pharmacology
  • Amphetamines / pharmacology
  • Animals
  • Corpus Striatum / drug effects*
  • Corpus Striatum / enzymology
  • Deoxyepinephrine / analogs & derivatives*
  • Deoxyepinephrine / pharmacology
  • Enzyme Activation
  • Hippocampus / drug effects*
  • Hippocampus / enzymology
  • In Vitro Techniques
  • Male
  • Methamphetamine / analogs & derivatives*
  • Methamphetamine / pharmacology
  • Oxidopamine / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Tryptophan Hydroxylase / metabolism*


  • Amphetamines
  • 2,4,5-trihydroxymethamphetamine
  • 2,4,5-trihydroxyamphetamine
  • alpha-methylepinine
  • Methamphetamine
  • Oxidopamine
  • Tryptophan Hydroxylase
  • Deoxyepinephrine
  • 5,6-Dihydroxytryptamine