PMID- 17640955
OWN - NLM
STAT- MEDLINE
DCOM- 20071212
LR  - 20181227
IS  - 0090-9556 (Print)
IS  - 0090-9556 (Linking)
VI  - 35
IP  - 10
DP  - 2007 Oct
TI  - Ambient temperature effects on 3,4-methylenedioxymethamphetamine-induced 
      thermodysregulation and pharmacokinetics in male monkeys.
PG  - 1840-5
AB  - Changes in ambient temperature are known to alter both the hyperthermic and the 
      serotonergic consequences of 3,4-methylenedioxymethamphetamine (MDMA). Metabolism 
      of MDMA has been suggested to be a requisite for these neurotoxic effects, 
      whereas the hyperthermic response is an important contributing variable. The aim 
      of the present study was to investigate the interaction between ambient 
      temperature, MDMA-induced thermodysregulation, and its metabolic disposition in 
      monkeys. MDMA (1.5 mg/kg i.v.) was administered noncontingently at cool (18 
      degrees C; n = 5), room (24 degrees C; n = 7), and warm (31 degrees C; n = 7) 
      ambient temperatures. For 240 min following MDMA administration, core temperature 
      was recorded and blood samples were collected for analysis of MDMA and its 
      metabolites 3,4-dihydroxymethamphetamine (HHMA), 3,4-dihydroxyamphetamine, and 
      3,4-methylenedioxyamphetamine (MDA). A dose of 1.5 mg/kg MDMA induced a 
      hypothermic response at 18 degrees C, a hyperthermic response at 31 degrees C, 
      and did not significantly change core temperature at 24 degrees C. Regardless of 
      ambient temperature, plasma MDMA concentrations reached maximum within 5 min, and 
      HHMA was a major metabolite. Curiously, the approximate elimination half-life 
      (t(1/2)) of MDMA at 18 degrees C (136 min) and 31 degrees C (144 min) was 
      increased compared with 24 degrees C (90 min) and is most likely because of 
      volume of distribution changes induced by core temperature alterations. At 18 
      degrees C, there was a significantly higher MDA area under the concentration-time 
      curve (AUC) and a trend for a lower HHMA AUC compared with 24 degrees C and 31 
      degrees C, suggesting that MDMA disposition was altered. Overall, induction of 
      hypothermia in a cool environment by MDMA may alter its disposition. These 
      results could have implications for MDMA-induced serotonergic consequences.
FAU - Banks, Matthew L
AU  - Banks ML
AD  - Department of Physiology and Pharmacology, Wake Forest University School of 
      Medicine, Winston-Salem, NC, USA.
FAU - Sprague, Jon E
AU  - Sprague JE
FAU - Kisor, David F
AU  - Kisor DF
FAU - Czoty, Paul W
AU  - Czoty PW
FAU - Nichols, David E
AU  - Nichols DE
FAU - Nader, Michael A
AU  - Nader MA
LA  - eng
GR  - F31 DA020281-01/DA/NIDA NIH HHS/United States
GR  - F31 DA020281-02/DA/NIDA NIH HHS/United States
GR  - F31 DA-020281/DA/NIDA NIH HHS/United States
GR  - P50 DA-06634/DA/NIDA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20070719
PL  - United States
TA  - Drug Metab Dispos
JT  - Drug metabolism and disposition: the biological fate of chemicals
JID - 9421550
RN  - 0 (Hallucinogens)
RN  - 0 (Serotonin Agents)
RN  - 15398-87-5 (alpha-methylepinine)
RN  - 4764-17-4 (3,4-Methylenedioxyamphetamine)
RN  - 555-64-6 (alpha-methyldopamine)
RN  - R7339QLN1C (Deoxyepinephrine)
SB  - IM
MH  - 3,4-Methylenedioxyamphetamine/blood/*pharmacokinetics/*pharmacology
MH  - Animals
MH  - Body Temperature/drug effects
MH  - Deoxyepinephrine/analogs & derivatives/blood
MH  - Fever/chemically induced/*metabolism
MH  - Hallucinogens/blood/pharmacokinetics/pharmacology
MH  - Macaca fascicularis
MH  - Male
MH  - Serotonin Agents/blood/pharmacokinetics/pharmacology
MH  - *Temperature
EDAT- 2007/07/21 09:00
MHDA- 2007/12/13 09:00
CRDT- 2007/07/21 09:00
PHST- 2007/07/21 09:00 [pubmed]
PHST- 2007/12/13 09:00 [medline]
PHST- 2007/07/21 09:00 [entrez]
AID - dmd.107.016261 [pii]
AID - 10.1124/dmd.107.016261 [doi]
PST - ppublish
SO  - Drug Metab Dispos. 2007 Oct;35(10):1840-5. doi: 10.1124/dmd.107.016261. Epub 2007 
      Jul 19.