NMDA Glutamate

Blocking the influx of Ca2+ions controlled via the glutamate NMDA receptor. 

Figure 11.2 The Ca2+ influx channels of the plasma membrane, (a) A voltage-gated channel—the membrane topography of the al-subunit, which forms the channel proper, (b) Membrane topography of TRP channels, homologous to the SOC channels, (c) Membrane topography of the ligand-gated glutamate NMDA receptor. (From Carafoli, 2005. Reproduced with permission from Blackwell...

Amino Acids Glutamate NMDA, AMPA, kainate Cation conductance... 

Several neurotransmitter and receptor changes are observed in Alzheimer s disease (Nordberg 1992). Losses occur in nicotinic receptors, but muscarinic receptors are relatively preserved. Reductions are also seen in serotonin 5-HTl and 5-HT2 receptors. Glutamate NMDA receptors decrease, while kainate receptors increase. j8-adrenergic and dopamine receptors are preserved. Decreases occur in receptors for somatostatin and neuropeptide Y, but corticotrophin-releasing factor receptors increase. Across all receptor subtypes for which there is a loss, the number of receptors decrease but the affinity constant remains unchanged. 

Several different types of serotonin receptor (for example, S-HTi / 5-HT2A/ 5-HT2C/ 5-HTib/id) have been associated with the motor side effects of the SSRIs which may arise should these drugs be administered in conjunction with a monoamine oxidase inhibitor. The 5-HT3 receptor is an example of a non-selective cation charmel receptor which is permeable to both sodium and potassium ions and, because both calcium and magnesium ions can modulate its activity, the 5-HT3 receptor resembles the glutamate-NMDA receptor. Antagonists of the 5-HT3 receptor, such as ondansetron, are effective antiemetics and are particularly useful when... 

Amantadine. Early or mild parkinsonian manifestations may be temporarily reUeved by amantadine. The underlying mechanism of action may involve, inter alia, blockade of Ugand-gated ion channels of the glutamate/ NMDA subtype, ultimately leading to a diminished release of acetylcholine. 

Glutamate systems have long been implicated in the pathophysiology of schizophrenia. Strong if circumstantial evidence comes from the psychosis associated with phencyclidine (PGP) administration PGP blocks of the ion channel the glutamate/NMDA receptor. Psychosis due to PGP and other noncompetitive NMDA antagonists includes the development of negative as well as positive symptoms and therefore is considered a better model of schizophre-... 

Ischemia Glutamate NMDA, AMPA (Haba et al., 1991 Phillis and O Regan, 1996 Olney et al., 1997)... 

Lapin I. P., Mirzaev S. M., Ryzov I. V., and Oxenkrug G. F. (1998). Anticonvulsant activity of melatonin against seizures induced by quinolinate, kainate, glutamate, NMDA, and pentylenete-trazole in mice. J. Pineal Res. 24 215-218. 

Mode of action. The precise mode of action of carbamazepine has not been fully established. It has been shown to stabilize both pre- and postsynaptic neurons by blocking the use and frequency-dependent sodium channels. While this is probably its main action, the blockade of the glutamate NMDA ionotropic receptors also leads to a reduction in the influx of sodium and calcium ions into the neuron. The net effect of these changes is a reduction in the sustained high-frequency repetitive firing of the action potentials which characterize epileptic activity. There is also evidence that carbamazepine blocks purine, noradrenaline, serotonin and muscarinic acetylcholine receptors which probably accounts for the use of carbamazepine as a mood stabilizing agent. 

NMDA receptors ( Figure 1.3-2) are the most complex of the ionotropic receptors. In addition to the recognition site for glutamate, NMDA receptors contain several allosteric modulatory sites, including (1) a site for the endogenous brain amino acids glycine and D-serine, (2) a polyamine-sensitive site, and (3) a redox site that is sensitive to glutathione (see Chapter 2.5 this volume). All sites act primarily to facilitate activity at the receptor. 

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