Role of hyperthermia in the protective action of clomethiazole against MDMA ('ecstasy')-induced neurodegeneration, comparison with the novel NMDA channel blocker AR-R15896AR

British Journal of Pharmacology
M I ColadoA R Green

Abstract

1. The immediate effect of administration of 3,4-methylenedioxymethamphetamine (MDMA or 'ecstasy') on rectal temperature and the effect of putative neuroprotective agents on this change has been examined in rats. The influence of the temperature changes on the long term MDMA-induced neurodegeneration of cerebral 5-hydroxytryptamine (5-HT) nerve terminals was also examined. 2. The novel low affinity N-methyl-D-aspartate (NMDA) receptor channel blocker AR-R15896AR (20 mg kg(-1), i.p.) given 5 min before and 55 min after MDMA (15 mg kg(-1), i.p.) did not prevent the MDMA-induced hyperthermia and did not alter either the MDMA-induced neurodegenerative loss of 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) in cortex, striatum and hippocampus or loss of [3H]-paroxetine binding in cortex 7 days later. 3. The neuroprotective agent clomethiazole (50 mg kg(-1), i.p.) given 5 min before and 55 min after MDMA (15 mg kg(-1)) abolished the MDMA-induced hyperthermic response and markedly attenuated the loss of 5-HT, 5-HIAA and [3H]-paroxetine binding in the brain regions examined 7 days later. 4. When rats treated with MDMA plus clomethiazole were kept at high ambient temperature for 5 h post-MDMA, thereby keeping their body temperature elevate...Continue Reading

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Citations

Apr 18, 2009·Molecular Neurobiology·João Paulo CapelaFélix Carvalho
Oct 3, 2002·European Journal of Pharmacology·Rachael M NelsonAtticus H Hainsworth
Aug 15, 2002·Pharmacology, Biochemistry, and Behavior·Erin M FalkJon E Sprague
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Apr 12, 2001·Journal of Neurochemistry·W L NixdorfB K Yamamoto
Jul 31, 2013·Life Sciences·Laura E HalpinBryan K Yamamoto
Dec 26, 2012·Neurotoxicology·Laura HondebrinkRemco H S Westerink
Nov 6, 2007·Neurotoxicology·C ChipanaE Escubedo
May 12, 2010·Basic & Clinical Pharmacology & Toxicology·Swapna KrishnamoorthyRui Tao
May 6, 2015·European Journal of Pharmacology·Stuart A CollinsBryan K Yamamoto
Jun 14, 2006·British Journal of Pharmacology·Esther O'SheaMaria Isabel Colado
Jul 19, 2003·Pharmacological Reviews·A Richard GreenM Isabel Colado
Jan 7, 2005·The Journal of Pharmacology and Experimental Therapeutics·Douglas C JonesTerrence J Monks
Oct 22, 2002·The Journal of Pharmacology and Experimental Therapeutics·Jie YuanGeorge A Ricaurte
Jun 3, 2016·Neurotoxicity Research·Pier Francesca PorcedduMicaela Morelli
Sep 24, 2021·Neurotoxicity Research·Jan van AmsterdamWim van den Brink

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