Glutamate / NMDA receptor

Krystal JH, Cramer JA, Krol WF, et al Naltrexone in the treatment of alcohol dependence. N Eng J Med 343 1734-1739, 2001 Krystal JH, Petrakis IL, Limoncelli D, et al Altered NMDA glutamate receptor antagonist response in recovering ethanol-dependent patients. Neuropsychopharmacology 28 2020-2028, 2003a... 

COXs thus catalyze the same first committed step of the AA cascade (Fig. 33-2). COX-2, however, is expressed in response to mitogenic and inflammatory stimuli and encoded by an early-response gene. To date we do not understand how COX-3 expression is regulated. In contrast, COX-1 expression is not subject to short-term regulation. Neurons in the hippocampus, as well as in a few other brain regions, are unlike other cells in that they display basal COX-2 expression [36]. This expression is modulated by synaptic activity, such as long-term potentiation, and involves the NMDA glutamate receptors [36,40]. 

Zorumski, C. F., Yamada, K. A., Price, M. T and Olney, J. W. (1993) A benzodiazepine recognition site associated with the non-NMDA glutamate receptor. Neuron 10,61-67. 

Eollowing chronic administration to rats, there is evidence that most antidepressants cause adaptive changes in S-HT a/ 5-HT2a alpha-1, alpha-2 and beta adrenoceptors, GABA-B receptors and possibly the NMDA-glutamate receptors. 

In experimental studies, chronic antidepressant treatments have been shown to reduce the behavioural effects of the NMDA-glutamate receptor antagonist dizolcipine. This suggests that antidepressants may act as functional NMDA receptor antagonists and thereby reduce excitatory glutamate transmission which is mediated by NMDA receptors. 

The mechanism of action of valproate is complex and still the subject of uncertainty. The drug appears to act by enhancing GABAergic function. Thus it increases GABA release, inhibits catabolism and increases the density of GABA-B receptors in the brain. There is also evidence that it increases the sensitivity of GABA receptors to the action of the inhibitory transmitter. Other actions that may contribute to its therapeutic effects include a decrease in dopamine turnover, a decrease in the activity of the NMDA-glutamate receptors and also a decrease in the concentration of... 

Sweat J (2001) The nem-onal MAP kinase cascade a biochemical signal integration system subserving synaptic plasticity and memory. J Neurochem 76 1-10 Szapiro G, Vianna MRM, McGaugh JL, Medina JH, Izquierdo 1 (2003) The role of NMDA glutamate receptors, PKA, MAPK, and CAMKll in the hippocampus in extinction of conditioned fear. Hippocampus 13 53-58... 

StrOhle A, Pasini A, Romeo E, Hermann B, Spalletta G, di Michele F, Holsboer F, Rupprecht R (2000) Fluoxetine decreases concentrations of 3a,5a-tetrahydrodeoxycorticosterone (3a,5a-THDOC) in major depression. J Psychiatr Res 34 183-186 StrOhle A, Kellner M, Holsboer F, Wiedemann K (2001) Anxiolytic activity of atrial natriuretic peptide in patients with panic disorder. Am J Psychiatry 158 1514-1516 StrOhle A, Romeo E, di Michele F, Pasini A, Yassouridis A, Holsboer F, Rupprecht R (2002) GABAA receptor modulatory neuroactive steroid composition in panic disorder and during paroxetine treatment. Am J Psychiatry 159 145-147 StrOhle A, Romeo E, di Michele F, Pasini A, Hermann B, Gajewsky G, Holsboer F, Rupprecht F (2003) Induced panic attacks shift GABAA receptor modulatory neuroactive steroid composition. Arch Gen Psychiatry 60 161-168 Szapiro G, Vianna MRM, McGaugh JL, Medina JH, Izquierdo I (2003) The role of NMDA glutamate receptors, PKA, MAPK, and CAMKII in the hippocampus in extinction of conditioned fear. Hippocampus 13 53-58... 

Acamprosate Antagonist of NMDA glutamate receptors May interfere with forms of synaptic plasticity that depend on NMDA receptors Treatment of alcoholism effective only in combination with counseling Allergic reactions, arrhythmia, and low or high blood pressure, headaches, insomnia, and impotence hallucinations, particularly in elderly patients... 

Leem, J. W., Choi, E. J., Park, E. S., Paik, K. S. N-methyl-D-aspartate (NMDA) and non-NMDA glutamate receptor antagonists differentially suppress dorsal horn neuron responses to mechanical stimuli in rats with peripheral nerve injury, Neurosci. Lett. 1996, 211, 37-40. 

Palazzo, E., Marabese, I., de Novellis, V., Oliva, P., Rossi, F., Berrino, L., Rossi, F., Maione, S. Metabotropic and NMDA glutamate receptors participate in the cannabinoid antinociception, Neuropharmacology 2001, 40, 319-326. 

FIGURE 10—25. Shown here is normal excitatory neurotransmission at the N-methyW-aspartate (NMDA) type of glutamate receptor. The NMDA receptor is a ligand-gated ion channel. This rapidly transmitting ion channel is an excitatory calcium channel. Occupancy of NMDA glutamate receptors by glutamate causes calcium channels to open and the neuron to be excited for neurotransmission. 

FIGURE 13—12. Pharmacology of phencyclidine (PCP). Phenylcyclidine is an open-channel antagonist of N-methyl-d-aspartate (NMDA) glutamate receptors at a site probably closely associated with the calcium ion channel there. This means that its site is probably inside the calcium channel, and it probably works best when the channel is open. 

Ananth C., Dheen S. T., Gopalakrishnakone R, and Kaur C. (2003a). Distribution of NADPH-diaphorase and expression of nNOS, N-methyl-D-aspartate receptor (NMDARl) and non-NMDA glutamate receptor (GlutR2) genes in the neurons of the hippocampus after domoic acid-induced lesions in adult rats. Hippocampus 13 260-272. 

It is well known that prolonged NMDA glutamate receptor activation results in degeneration of neurons (excitotoxicity). This has been attributed to a large increase in calcium influx, which activates the calmodulin-dependent NOS-1 and leads to sustained elevation of nitric oxide concentrations. The increase in neurodegeneration caused by excitatory amino acids may be due to enhanced oxygen radical formation since superoxide dismutase has a beneficial effect in... 

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