NONCOMPETITIVE NMDA RECEPTOR ANTAGONISTS WITH FAST OPEN-CHANNEL BLOCKING KINETICS AND STRONG VOLTAGE-DEPENDENCY AS POTENTIAL THERAPEUTIC AGENTS FOR ALZHEIMERS DEMENTIA

There is a growing body of evidence that disturbances of glutamatergic neurotransmission may underlie the pathomechanism and cognitive defic its of Alzheimer's disease, This review describes the potential use of low affinity, noncompetitive NMDA receptor antagonists in the treatme nt of this disease using memantine as an example, Evidence is presente d indicating that this class of compound is neuroprotective in preclin ical models of subchronic glutamate toxicity without producing side ef fects characteristic for other classes of NMDA receptor antagonist Thi s is attributed to their fast blocking kinetics and strong voltage dep endency, Memantine also produces symptomatological improvement of cogn ition in animal models, The mechanism of action of this effect is stil l unclear but might be related to an enhancement of AMPA receptor medi ated neurotransmission. In patients with dementia syndrome of various aetiologies, memantine produces a rapid onset, clinical improvement in various symptomatological deficits.