PMID- 1349640
OWN - NLM
STAT- MEDLINE
DCOM- 19920605
LR  - 20131121
IS  - 0022-3565 (Print)
IS  - 0022-3565 (Linking)
VI  - 261
IP  - 2
DP  - 1992 May
TI  - Effects of 3,4-dihydroxymethamphetamine and 2,4,5-trihydroxymethamphetamine, two 
      metabolites of 3,4-methylenedioxymethamphetamine, on central serotonergic and 
      dopaminergic systems.
PG  - 447-53
AB  - The effects of 3,4-dihydroxymethamphetamine (DHM) and 
      2,4,5-trihydroxymethamphetamine (THM) on central serotonergic and dopaminergic 
      systems were investigated to determine if these metabolites share the 
      neurochemical properties of 3,4-methylenedioxymethamphetamine. THM (50-200 
      micrograms) or DHM (135 micrograms) was administered i.c.v. to rats; 5 days 
      later, cortical, striatal and hippocampal tryptophan hydroxylase (TPH) activity 
      were decreased by THM in a dose-dependent manner, whereas DHM was without effect 
      in these brain structures. The concentration of serotonin in the brain structures 
      contralateral to the side of THM injection was also decreased, but to a lesser 
      degree. THM (100 and 200 micrograms) increased TPH activity to 155% of control in 
      the dorsal raphe, whereas a dose of 50 micrograms increased TPH activity to 132% 
      of control in the median raphe nucleus. THM also markedly reduced striatal 
      tyrosine hydroxylase activity, but did not alter enzyme activity in the 
      substantia nigra; DHM increased striatal tyrosine hydroxylase activity to 115% of 
      control. These results suggest that THM, but not DHM, is toxic to both 
      dopaminergic and serotonergic nerve terminals. Although THM could not be 
      established as the neurotoxic metabolite explaining 
      3,4-methylenedioxymethamphetamine (MDMA) toxicity, its properties may prove 
      useful in elucidating amphetamine toxicity.
FAU - Johnson, M
AU  - Johnson M
AD  - Department of Pharmacology and Toxicology, University of Utah, Salt Lake City.
FAU - Elayan, I
AU  - Elayan I
FAU - Hanson, G R
AU  - Hanson GR
FAU - Foltz, R L
AU  - Foltz RL
FAU - Gibb, J W
AU  - Gibb JW
FAU - Lim, H K
AU  - Lim HK
LA  - eng
GR  - DA 00869/DA/NIDA NIH HHS/United States
GR  - DA 04221/DA/NIDA NIH HHS/United States
GR  - DA 05860/DA/NIDA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Pharmacol Exp Ther
JT  - The Journal of pharmacology and experimental therapeutics
JID - 0376362
RN  - 136706-32-6 (2,4,5-trihydroxymethamphetamine)
RN  - 333DO1RDJY (Serotonin)
RN  - 44RAL3456C (Methamphetamine)
RN  - 4764-17-4 (3,4-Methylenedioxyamphetamine)
RN  - EC 1.14.16.4 (Tryptophan Hydroxylase)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
RN  - VTD58H1Z2X (Dopamine)
SB  - IM
MH  - 3,4-Methylenedioxyamphetamine/*analogs & derivatives/*metabolism/pharmacology
MH  - Animals
MH  - Brain/*drug effects/enzymology
MH  - Chromatography, High Pressure Liquid
MH  - Dopamine/*metabolism
MH  - Injections, Intraventricular
MH  - Male
MH  - Methamphetamine/*analogs & derivatives/pharmacology
MH  - N-Methyl-3,4-methylenedioxyamphetamine
MH  - Rats
MH  - Rats, Inbred Strains
MH  - Serotonin/*metabolism
MH  - Tryptophan Hydroxylase/metabolism
EDAT- 1992/05/01 00:00
MHDA- 1992/05/01 00:01
CRDT- 1992/05/01 00:00
PHST- 1992/05/01 00:00 [pubmed]
PHST- 1992/05/01 00:01 [medline]
PHST- 1992/05/01 00:00 [entrez]
PST - ppublish
SO  - J Pharmacol Exp Ther. 1992 May;261(2):447-53.