Influence of memantine on brain monoaminergic neurotransmission parameters in mice: neurochemical and behavioral study. 
Memantine, a non-competitive antagonist of NMDA receptors, has recently been used in Alzheimer's disease.  The influences of memantine on behavioral changes, monoamine oxidase (MAO) activity and reuptake of both serotonin (5-HT) and dopamine in mice were examined in the present study.  Memantine dose-dependently increased locomotor activity.  This effect was inhibited by intraperitoneal (i.p.)  administration of haloperidol.  Furthermore, administration [intracerebroventricular (i.c.v.)]  of memantine did not induce the head-twitch response (HTR).  However, the 5-HT-induced HTR was potentiated by the combined administration of memantine.  The enhanced HTR was inhibited by i.p.  administration of haloperidol or 5-HT(2A) antagonist ketanserin.  Memantine at 1 mM inhibited both MAO-A and MAO-B activities in mouse forebrain homogenates to 37% and 64% of controls, respectively.  Lineweaver-Burk plots analysis revealed competitive inhibition with both MAO-A and MAO-B. The inhibitions were also reversible.  Memantine inhibited the reuptake of both 5-HT and dopamine into mouse forebrain synaptosomes.  5-HT and dopamine reuptakes were inhibited to 2% and 16% of controls, respectively, with 1 mM memantine.  These findings suggest that the increased locomotor activity and enhanced 5-HT-induced HTR by memantine may result from the reuptake and turnover inhibitions of 5-HT and dopamine.