PMID- 1676172
OWN - NLM
STAT- MEDLINE
DCOM- 19910731
LR  - 20190712
IS  - 0091-3057 (Print)
IS  - 0091-3057 (Linking)
VI  - 38
IP  - 2
DP  - 1991 Feb
TI  - Assessment of the role of alpha-methylepinine in the neurotoxicity of MDMA.
PG  - 345-51
AB  - To assess the potential involvement of metabolism of 
      3,4-methylenedioxymethamphetamine (MDMA) to the catechol alpha-methylepinine in 
      producing serotonergic neurotoxicity, we attempted to correlate aspects of this 
      reaction with the neurotoxicity profile of MDMA. In contrast to the 
      stereoselectivity of S-(+)-MDMA in causing persistent declines in rat brain 
      5-hydroxyindole levels, no stereochemical component to the metabolic reaction was 
      apparent. Rat liver microsomes generated a significantly greater amount of 
      alpha-methylepinine than did mouse microsomes, but similar amounts of metabolite 
      were produced by brain microsomes from the two species. Formation of 
      alpha-methylepinine by hepatic, but not brain, microsomes was inhibited by SKF 
      525A and induced by phenobarbital, possibly indicating a tissue specificity in 
      cytochrome P-450-dependent metabolism of MDMA. To directly assess whether 
      alpha-methylepine is a likely mediator of MDMA neurotoxicity, the compound was 
      administered intracerebroventricularly. No persistent declines in biogenic amines 
      or their metabolites were observed one week following treatment. These data 
      suggest that alpha-methylepinine alone is not responsible for the neurotoxic 
      effects of MDMA.
FAU - Steele, T D
AU  - Steele TD
AD  - Department of Pharmacology and Toxicology, School of Pharmacy and Pharmacal 
      Sciences, Purdue University, West Lafayette, IN 47907.
FAU - Brewster, W K
AU  - Brewster WK
FAU - Johnson, M P
AU  - Johnson MP
FAU - Nichols, D E
AU  - Nichols DE
FAU - Yim, G K
AU  - Yim GK
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Pharmacol Biochem Behav
JT  - Pharmacology, biochemistry, and behavior
JID - 0367050
RN  - 0 (Biogenic Amines)
RN  - 15398-87-5 (alpha-methylepinine)
RN  - 4764-17-4 (3,4-Methylenedioxyamphetamine)
RN  - 9035-51-2 (Cytochrome P-450 Enzyme System)
RN  - A510CA4CBT (Proadifen)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
RN  - R7339QLN1C (Deoxyepinephrine)
RN  - YQE403BP4D (Phenobarbital)
SB  - IM
MH  - 3,4-Methylenedioxyamphetamine/administration & dosage/*analogs & 
      derivatives/metabolism/toxicity
MH  - Animals
MH  - Biogenic Amines/metabolism
MH  - Brain Chemistry/drug effects
MH  - Chromatography, High Pressure Liquid
MH  - Cytochrome P-450 Enzyme System/metabolism
MH  - Deoxyepinephrine/administration & dosage/*analogs & 
      derivatives/metabolism/toxicity
MH  - Electrochemistry
MH  - Injections, Intraventricular
MH  - Male
MH  - Mice
MH  - Microsomes, Liver/drug effects/enzymology
MH  - N-Methyl-3,4-methylenedioxyamphetamine
MH  - Nervous System Diseases/*chemically induced/physiopathology
MH  - Phenobarbital/pharmacology
MH  - Proadifen/pharmacology
MH  - Rats
MH  - Rats, Inbred Strains
MH  - Species Specificity
EDAT- 1991/02/01 00:00
MHDA- 1991/02/01 00:01
CRDT- 1991/02/01 00:00
PHST- 1991/02/01 00:00 [pubmed]
PHST- 1991/02/01 00:01 [medline]
PHST- 1991/02/01 00:00 [entrez]
AID - 0091-3057(91)90289-E [pii]
AID - 10.1016/0091-3057(91)90289-e [doi]
PST - ppublish
SO  - Pharmacol Biochem Behav. 1991 Feb;38(2):345-51. doi: 
      10.1016/0091-3057(91)90289-e.