Glutamatergic systems

Excitotoxicity is the over-activity of the glutamatergic system responsible for the large number of dead neurons observed after ischemia (stroke) or epileptic seizures. This neuronal death is due to an overexcitation of the neurons and the massive Ca2+ entry... 

Allison C, Pratt JA Neuroadaptive processes in GABAergic and glutamatergic systems in benzodiazepine dependence. Pharmacol Ther 98 171-195, 2003... 

Although, to our knowledge, the effects of inhalation of amyl nitrite or butyl nitrite on glutamatergic neurotransmission have not been studied, NO, the potent compound that mediates the peripheral effects of nitrites in blood vessels, if released in the CNS when nitrites are inhaled, may potentially affect the glutamatergic system. NO has been reported to act directly on the postsynaptic NMDA receptor, where it can increase or decrease NMDA-mediated currents and subsequent calcium influx (Aizenman et al. 1990 Dingledine et al. 1999 Manzoni et al. 1992). 

Guilarte TR. 1997. Glutamatergic system and developmental lead neurotoxicity. Neurotoxicology 18(3) 665-672. 

The antidepressant effects reported for some drugs that antagonize NMDA receptors suggest a role for the glutamatergic system in depressive disorders 892... 

Cacabelos, R., Takeda, M., Winblad, B. (1999) The glutamatergic system and neurodegeneration in dementia preventive strategies in Alzheimer disease. Int. J. Geriatr. Psychiatry, 14, 3-47. 

Memantine is the first in a novel class of Alzheimer s disease medications acting a.o. on the NMDA receptor of the glutamatergic system. It also acts as an uncompetitive antagonist at different neuronal nicotinic receptors at potencies possibly similar to the NMDA receptor. Memantine is approved for treatment of moderate to severe Alzheimer s disease and its use is associated with a moderate decrease in clinical deterioration of the disease. Common adverse drug reactions (>1% of patients) include confusion, dizziness, drowsiness, headache, insomnia, agitation, and/or hallucinations. 

S. Characterization of the glutamatergic system for induction and maintenance of allodynia, Brain Res. 2001, 895, 178-185. 

Recently, attempts have been made to reconcile the deficiencies in the dopamine hypothesis by focusing on other neurotransmitters that may interact with dopamine in discrete cortical and subcortical neural circuits. In particular, the involvement of the glutamatergic system has received considerable attention. This possibility has arisen from the finding that dissociation anaesthetics such as ketamine and phencyclidine (PCP) can cause a schizophreniform psychosis in normal individuals. Such effects bear a much closer resemblance to the positive and negative symptoms of... 

Side effects. The most common side effects are headache, nausea and vomiting, diplopia, dizziness, ataxia and tremor. There are also reports that lamotrigine can cause such psychiatric side effects as aggression, agitation, confusion, hallucinations and psychosis, some of these effects possibly being associated with a reduction in the glutamatergic system. Rashes are a frequent side effect, occurring in up to 5% of patients. Usually rashes are mild but occasionally can be severe and amount to a Stevens-Johnson syndrome. The severe rash occurs more commonly in children. 

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