Memantine attenuates 3,4-methylenedioxymethamphetamine-induced hyperthermia in rats.
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 mgkg) either before or after MDMA (10 mgkg) administration significantly decreased the peak body temperature. Results from our microdialysis study indicated that pretreatment with memantine (20 mgkg) 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 mgkg) and the competitive NMDA antagonist CGS 19755 (5 mgkg), but not by the selective α-7 nAChR antagonist methyllycaconitine (6 or 10 mgkg). 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.