PMID- 2576302
OWN - NLM
STAT- MEDLINE
DCOM- 19900412
LR  - 20141120
IS  - 0161-813X (Print)
IS  - 0161-813X (Linking)
VI  - 10
IP  - 3
DP  - 1989 Fall
TI  - Influence of inducers and inhibitors on the metabolism in vitro and neurochemical 
      effects in vivo of MDMA.
PG  - 455-66
AB  - (S)-(+)- and (R)-(-)-3,4-methylenedioxymethamphetamine (MDMA) were metabolized in 
      vitro by rat liver microsomes via N-demethylation to 
      3,4-methylenedioxyamphetamine (MDA). Whereas no difference was found in the 
      biotransformation of the two enantiomers in the male rat or in the phenobarbital 
      (PB) treated animals of either sex, more than twice as much MDA was formed from 
      (S)-(+)- than from (R)-(-)-MDMA in the untreated female rat. Although 
      3-methylcholanthrene (3MC) pretreated rat liver microsomes were less active than 
      those from the untreated rats of the same sex, they formed more MDA from (+)- 
      than from (-)-MDMA. The enantioselective metabolism thus appears to be associated 
      with the relative abundance of individual cytochrome P-450 isozymes. (S)-(+)- and 
      (R)-(-)-MDMA.HCl (20 mg/kg) were about equipotent in depleting serotonin (5-HT) 
      levels in the frontal cortex at 3 hrs and 1 wk following oral administration to 
      female rats. Pretreatment of rats with SKF-525A attenuated and that with PB 
      enhanced the 5-HT depleting potential of either isomer at 3 hrs. The 5-HT 
      depleting potency of (+)-MDMA was significantly greater than that of its 
      (-)-antipode at 3 hr in PB pretreated, but not in SKF-525A pretreated animals. 
      The results suggest that the neurochemical effects of MDMA are caused by the 
      formation of an active metabolite in vivo, and since both enantiomers were 
      N-demethylated in vitro to approximately the same extent by PB pretreated rat 
      liver microsomes, the active metabolite may be other than MDA.
FAU - Gollamudi, R
AU  - Gollamudi R
AD  - Department of Medicinal Chemistry, College of Pharmacy, University of Tennessee, 
      Memphis 38163.
FAU - Ali, S F
AU  - Ali SF
FAU - Lipe, G
AU  - Lipe G
FAU - Newport, G
AU  - Newport G
FAU - Webb, P
AU  - Webb P
FAU - Lopez, M
AU  - Lopez M
FAU - Leakey, J E
AU  - Leakey JE
FAU - Kolta, M
AU  - Kolta M
FAU - Slikker, W Jr
AU  - Slikker W Jr
LA  - eng
PT  - Journal Article
PL  - Netherlands
TA  - Neurotoxicology
JT  - Neurotoxicology
JID - 7905589
RN  - 0 (Amphetamines)
RN  - 0 (Neurotransmitter Agents)
RN  - 0 (Proteins)
RN  - 333DO1RDJY (Serotonin)
RN  - 4764-17-4 (3,4-Methylenedioxyamphetamine)
RN  - A510CA4CBT (Proadifen)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
RN  - YQE403BP4D (Phenobarbital)
SB  - IM
MH  - 3,4-Methylenedioxyamphetamine/analogs & derivatives/*metabolism/pharmacology
MH  - Amphetamines/*metabolism
MH  - Animals
MH  - Biotransformation
MH  - Brain Chemistry/*drug effects
MH  - Cerebral Cortex/drug effects/metabolism
MH  - Dealkylation
MH  - Female
MH  - In Vitro Techniques
MH  - Male
MH  - Mass Spectrometry
MH  - Microsomes, Liver/metabolism
MH  - N-Methyl-3,4-methylenedioxyamphetamine
MH  - Neurotransmitter Agents/metabolism
MH  - Phenobarbital/pharmacology
MH  - Proadifen/pharmacology
MH  - Proteins/metabolism
MH  - Rats
MH  - Rats, Inbred Strains
MH  - Serotonin/metabolism
MH  - Stereoisomerism
EDAT- 1989/01/01 00:00
MHDA- 2001/03/28 10:01
CRDT- 1989/01/01 00:00
PHST- 1989/01/01 00:00 [pubmed]
PHST- 2001/03/28 10:01 [medline]
PHST- 1989/01/01 00:00 [entrez]
PST - ppublish
SO  - Neurotoxicology. 1989 Fall;10(3):455-66.