PMID- 17320075
OWN - NLM
STAT- MEDLINE
DCOM- 20070621
LR  - 20171116
IS  - 0014-2999 (Print)
IS  - 0014-2999 (Linking)
VI  - 562
IP  - 3
DP  - 2007 May 21
TI  - Studies on the mechanisms underlying amiloride enhancement of 
      3,4-methylenedioxymethamphetamine-induced serotonin depletion in rats.
PG  - 198-207
AB  - Amiloride and several of its congeners known to block the Na(+)/Ca(2+) and/or 
      Na(+)/H(+) antiporters potentiate methamphetamine-induced neurotoxicity without 
      altering methamphetamine-induced hyperthermia. We now examine whether amiloride 
      also exacerbates 3,4-methylenedioxymethamphetamine (MDMA)-induced long-term 
      serotonin (5-HT) loss in rats. Amiloride (2.5 mg/kg, every 2 h x 3, i.p.) given 
      at ambient temperature 30 min before MDMA (5 mg/kg, every 2 h x 3, i.p.), 
      markedly exacerbated long-term 5-HT loss. However, in contrast to 
      methamphetamine, amiloride also potentiated MDMA-induced hyperthermia. Fluoxetine 
      (10 mg/kg i.p.) completely protected against 5-HT depletion caused by the 
      MDMA/amiloride combination without significantly altering the hyperthermic 
      response. By contrast, the calcium channel antagonists flunarizine or diltiazem 
      did not afford any protection. Findings with MDMA and amiloride were extended to 
      the highly selective Na(+)/H(+) exchange inhibitor dimethylamiloride, suggesting 
      that the potentiating effects of amiloride are probably mediated by the blockade 
      of Na(+)/H(+) exchange. When the MDMA/amiloride combination was administered at 
      15 degrees C hyperthermia did not develop and brain 5-HT concentrations remained 
      unchanged 7 days later. Intrastriatal perfusion of MDMA (100 microM for 8 h) in 
      combination with systemic amiloride caused a small depletion of striatal 5-HT 
      content in animals made hyperthermic but not in the striatum of normothermic 
      rats. These data suggest that enhancement of MDMA-induced 5-HT loss caused by 
      amiloride or dimethylamiloride depends on their ability to enhance MDMA-induced 
      hyperthermia. We hypothesise that blockade of Na(+)/H(+) exchange could synergize 
      with hyperthermia to render 5-HT terminals more vulnerable to the toxic effects 
      of MDMA.
FAU - Goni-Allo, Beatriz
AU  - Goni-Allo B
AD  - Department of Pharmacology, School of Medicine, University of Navarra, C/ 
      Irunlarrea, 1, 31008, Pamplona, Spain.
FAU - Puerta, Elena
AU  - Puerta E
FAU - Hervias, Isabel
AU  - Hervias I
FAU - Di Palma, Richard
AU  - Di Palma R
FAU - Ramos, Maria
AU  - Ramos M
FAU - Lasheras, Berta
AU  - Lasheras B
FAU - Aguirre, Norberto
AU  - Aguirre N
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20070201
PL  - Netherlands
TA  - Eur J Pharmacol
JT  - European journal of pharmacology
JID - 1254354
RN  - 0 (Hallucinogens)
RN  - 0 (Serotonin Agents)
RN  - 0 (Sodium Channel Blockers)
RN  - 0 (Sodium-Hydrogen Exchangers)
RN  - 333DO1RDJY (Serotonin)
RN  - 3GC547293P (5-dimethylamiloride)
RN  - 7DZO8EB0Z3 (Amiloride)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
SB  - IM
MH  - Amiloride/analogs & derivatives/*pharmacology
MH  - Animals
MH  - Body Temperature/drug effects
MH  - Corpus Striatum/drug effects/metabolism
MH  - Drug Synergism
MH  - Fever/chemically induced
MH  - Hallucinogens/*pharmacology
MH  - Male
MH  - N-Methyl-3,4-methylenedioxyamphetamine/*pharmacology
MH  - Rats
MH  - Rats, Wistar
MH  - Serotonin/*metabolism
MH  - Serotonin Agents/*pharmacology
MH  - Sodium Channel Blockers/*pharmacology
MH  - Sodium-Hydrogen Exchangers/antagonists & inhibitors/drug effects/physiology
EDAT- 2007/02/27 09:00
MHDA- 2007/06/22 09:00
CRDT- 2007/02/27 09:00
PHST- 2006/08/31 00:00 [received]
PHST- 2006/12/13 00:00 [revised]
PHST- 2007/01/11 00:00 [accepted]
PHST- 2007/02/27 09:00 [pubmed]
PHST- 2007/06/22 09:00 [medline]
PHST- 2007/02/27 09:00 [entrez]
AID - S0014-2999(07)00098-2 [pii]
AID - 10.1016/j.ejphar.2007.01.049 [doi]
PST - ppublish
SO  - Eur J Pharmacol. 2007 May 21;562(3):198-207. doi: 10.1016/j.ejphar.2007.01.049. 
      Epub 2007 Feb 1.