NMDA cognitive

Other systems also interact with glutamate. Activation of L-type voltagegated calcium channels (VGCC) occurs with NMDA receptor activation. Lamotrigine blocks several ion channels, including P- and N-type VGCC channels, an action that blocks the euphoric effects of ketamine and reduces dysphoric and cognitive effects (Hundt et al. 1998). Other modulatory sites,... 

The current gold standard of treatment for cognitive symptoms includes pharmacologic management with a cholinesterase inhibitor and/or an N-methyl-D-aspartate (NMDA) antagonist. 

Meman- tine NMDA antagonist APOE PSl PS2 Prospective Apoptosis related Cognition One study Gene-to-gene analysis... 

Recent studies have identified abnormalities associated with schizophrenia that interfere with the activation of the glycine modulatory site of the NMDA receptor (Coyle and Tsai 2004). Further, the use of NMDA receptor glycine site agonists such as glycine, o-serine or o-cycloserine in clinical trials has demonstrated some efficacy in ameliorating the negative symptoms and cognitive disabihties in schizophrenics (Coyle and Tsai 2004). 

Glutamate was initially implicated in schizophrenia by studies of the behavioral effects of N-methyl-D-aspartate (NMDA) receptor antagonists (e.g., PCP, ketamine), which produce psychotic symptoms and cognitive dysfunction in healthy subjects and exacerbate psychotic, negative, and cognitive symptoms in patients with schizophrenia. Studies show that acute administration of NMDA antagonists causes NMDA receptor dysfunction, resulting in decreased inhibition of subcortical dopamine neurons and consequent increased mesolimbic dopamine release. Chronic administration produces decreased release, or hypoactivity, of dopamine in the prefrontal cortex (Davis and Lieberman, 2000). 

D-Cycloserine is a central partial agonist of NMDA receptors in place of P-glycine, which in low doses has shown an antagonism of cognitive deterioration induced by scopolamine. Confusion, disorientation, and memory loss have been observed at high doses. D-Cycloserine can provide a symptomatic treatment of AD at low dosage (Bowen et al. 1992 B. L. Schwartz et al. 1996). 

In this chapter, we use the term cognitive enhancers to refer to two classes of pharmacological agents used in the treatment of Alzheimer s disease the cholinesterase inhibitors and the A-methyl-D-aspartate (NMDA) receptor antagonists. 

It seems that altered intracellular calcium homeostasis may be a crucial event in the initiation and progression of AD however the therapeutic value has thus far been mixed. For example, the use of calcium channel blockers, including dihydropy-ridines and non-dihydropyridines, has no effect on the risk of AD (Yasar et al., 2005), whereas the NMDA-antagonist memantine improves cognition in mild to moderate AD (Peskind et al., 2006). 

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