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Memantine as a reversible MAO Inhibitor?

Posted by Rosy Crucifiction on October 15, 2009, at 13:07:33

I'd appreciate any comments. This seems to be saying memantine (in mouse models) is a reversible MAO inhibitor. They hypothesize MAO inhibition in humans:
"Thus, it is plausible that peripheral administration of memantine may inhibit MAO activity in the human brain, as well as having effects through NMDA receptor antagonism."

Influence of Memantine on Brain Monoaminergic Neurotransmission - Parameters in Mice: Neurochemical and Behavioral Study

Hiroshi ONOGI,aSeiichiro ISHIGAKI,bOsamu NAKAGAWASAI,*,aYumiko ARAI-KATO,cYuichiro ARAI,d,1) Hiromi WATANABE,aAtsushi MIYAMOTO,eKoichi TAN-NO,and Takeshi TADANO

"Memantine, a non-competitive antagonist of NMDA receptors, has recently been used in Alzheimers dis- ease. 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-HT2Aantagonist ketanserin. Memantine at 1mM inhibited both MAO-A and MAO-B activities in mouse forebrain homogenates to 37% and 64% of controls, respectively. LineweaverBurk 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 1mMmemantine. 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."

download whole article here:http://www.jstage.jst.go.jp/article/bpb/32/5/850/_pdf


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poster:Rosy Crucifiction thread:921016
URL: http://www.dr-bob.org/babble/20091012/msgs/921016.html