PMID- 10494994
OWN - NLM
STAT- MEDLINE
DCOM- 19991021
LR  - 20190712
IS  - 0091-3057 (Print)
IS  - 0091-3057 (Linking)
VI  - 64
IP  - 1
DP  - 1999 Sep
TI  - Acute toxicity of 3,4-methylenedioxymethamphetamine (MDMA) in Sprague-Dawley and 
      Dark Agouti rats.
PG  - 29-34
AB  - Ingestion of MDMA ("ecstasy") by humans can cause acute toxicity manifested by 
      hyperthermia and death. Demethylenation of MDMA is catalyzed by cytochrome P-450 
      2D6 (CYP2D6) and cytochrome P-450 2D1 (CYP2D1) in humans and rats, respectively, 
      and is polymorphically expressed. It has been proposed that CYP2D6 deficiency may 
      account for the unexplained toxicity of MDMA. The female Dark Agouti rat is 
      deficient in CYP2D1, and serves as a model for the human poor metabolizer. We 
      investigated thermogenic and locomotor actions of MDMA in adult female 
      Sprague-Dawley (CYP2D1 replete) and Dark Agouti rats. MDMA (2, 5, and 10 mg/kg) 
      and saline were injected subcutaneously at ambient temperatures of 22 and 31 
      degrees C. There was no difference in core temperature responses between the two 
      rat strains. Hypothermia occurred in the first 30 min and temperature elevation 
      thereafter. MDMA increased locomotor activity in Sprague-Dawley but not in Dark 
      Agouti rats. However, MDMA had pronounced lethal effects at 31 degrees C ambient 
      in the Dark Agouti rats only. We conclude that the poor metaboliser phenotype may 
      predispose to lethality, but the mechanism is as yet unknown.
FAU - Malpass, A
AU  - Malpass A
AD  - Department of Clinical & Experimental Pharmacology, University of Adelaide, SA, 
      Australia.
FAU - White, J M
AU  - White JM
FAU - Irvine, R J
AU  - Irvine RJ
FAU - Somogyi, A A
AU  - Somogyi AA
FAU - Bochner, F
AU  - Bochner F
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Pharmacol Biochem Behav
JT  - Pharmacology, biochemistry, and behavior
JID - 0367050
RN  - 0 (Hallucinogens)
RN  - 9035-51-2 (Cytochrome P-450 Enzyme System)
RN  - EC 1.1.- (Alcohol Oxidoreductases)
RN  - EC 1.14.14.1 (Aryl Hydrocarbon Hydroxylases)
RN  - EC 1.14.14.1 (Cyp2d1 protein, rat)
RN  - EC 1.14.14.1 (Cytochrome P-450 CYP2D6)
RN  - EC 1.14.14.1 (Cytochrome P450 Family 2)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
SB  - IM
MH  - Alcohol Oxidoreductases
MH  - Animals
MH  - *Aryl Hydrocarbon Hydroxylases
MH  - Body Temperature Regulation/drug effects
MH  - Cytochrome P-450 CYP2D6/metabolism
MH  - Cytochrome P-450 Enzyme System/metabolism
MH  - Cytochrome P450 Family 2
MH  - Female
MH  - Hallucinogens/metabolism/*toxicity
MH  - Motor Activity/drug effects
MH  - N-Methyl-3,4-methylenedioxyamphetamine/metabolism/*toxicity
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Species Specificity
EDAT- 1999/09/24 00:00
MHDA- 1999/09/24 00:01
CRDT- 1999/09/24 00:00
PHST- 1999/09/24 00:00 [pubmed]
PHST- 1999/09/24 00:01 [medline]
PHST- 1999/09/24 00:00 [entrez]
AID - S0091-3057(99)00116-1 [pii]
AID - 10.1016/s0091-3057(99)00116-1 [doi]
PST - ppublish
SO  - Pharmacol Biochem Behav. 1999 Sep;64(1):29-34. doi: 
      10.1016/s0091-3057(99)00116-1.