title: Memantine attenuates 3,4-methylenedioxymethamphetamine-induced hyperthermia in rats.
abstract: 3,4-Methylenedioxymethamphetamine (MDMA) is an illegal drug that can induce life-threatening hyperthermia. No effective pharmacological treatment for MDMA-induced hyperthermia has yet been established. We investigated the effects of memantine, a non-competitive N-methyl-D-aspartate (NMDA)-type glutamate receptor antagonist and an α-7 nicotinic acetylcholine receptor (nAChR) antagonist, on MDMA-induced hyperthermia in rats. Treatment of animals with memantine (10 or 20 mg/kg) either before or after MDMA (10 mg/kg) administration significantly decreased the peak body temperature. Results from our microdialysis study indicated that pretreatment with memantine (20 mg/kg) before MDMA administration had no effect on the MDMA-induced increase in serotonin (5-HT) and dopamine (DA) levels in the anterior hypothalamus. MDMA-induced hyperthermia was significantly suppressed by pretreatment with the non-competitive NMDA receptor antagonist MK-801 (0.5 mg/kg) and the competitive NMDA antagonist CGS 19755 (5 mg/kg), but not by the selective α-7 nAChR antagonist methyllycaconitine (6 or 10 mg/kg). These results indicate that the inhibitory effect of memantine on MDMA-induced hyperthermia may be due to its activity as an NMDA receptor antagonist and not as a result of a direct effect on the 5-HT or DA systems. The present study suggests that moderate doses of memantine may be useful for the treatment of MDMA-induced hyperthermia in humans.
authors.affiliation: Department of Psychiatry, Jichi Medical University, Tochigi, Japan. midorin@jichi.ac.jp
authors.forename: Koichi
authors.initials: K
authors.lastname: Nisijima
authors.forename: Kyoko
authors.initials: K
authors.lastname: Kuboshima
authors.forename: Katsutoshi
authors.initials: K
authors.lastname: Shioda
authors.forename: Tatuki
authors.initials: T
authors.lastname: Yoshino
authors.forename: Tatsunori
authors.initials: T
authors.lastname: Iwamura
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kato
mesh_terms: D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D004298:Dopamine / Q000032:analysis / Q000378:metabolism; D015259:Dopamine Agents / Q000494:pharmacology*; D005334:Fever / Q000139:chemically induced / Q000188:drug therapy*; D006213:Hallucinogens / Q000633:toxicity*; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008559:Memantine / Q000494:pharmacology*; D017551:Microdialysis; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000032:analysis / Q000378:metabolism
chemical_list: D015259:Dopamine Agents; D006213:Hallucinogens; D012701:Serotonin; D018817:N-Methyl-3,4-methylenedioxyamphetamine; D004298:Dopamine; D008559:Memantine