Glutamate system

Clearly there is much therapeutic potential for drugs acting on glutamate systems but much more progress is needed. 

Thus there is evidence, albeit circumstantial, of a disturbance of glutamate systems in the disease. In addition there is evidence of GABAergic deficits. Adding to the relevance of these hypotheses of amino acid transmitter dysfunction is the opportunity to relate neurochemical changes directly to a neuronal pathology and, with some further extrapolation, to the aetiology of schizophrenia. 

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-... 

Abnormalities of the glutamate system have also been documented in neuropsychiatric disorders. For example, compounds such as PCP and ketamine, which block the NMDA receptor, can induce psychotic symptoms. By contrast, compounds such as d-cycloserine or glycine, which increase NMDA receptor function via the glycine binding site, can decrease psychotic and/or negative symptoms in schizophrenia (Farber et ah, 1999 Goff et ah, 1999, Fleresco-Levy et ah, 1999). 

Acamprosate (calcium acetylhomotaurine) has a chemical structure similar to homotaurine and GABA and appears to normalize N-methyl-D-aspartate (NMDA) receptor tone in the glutamate system. 

In addition to an abnormality in the corticostriatal system, it is also possible that a disorder in the dopamine-glutamate system occurs in other subcortical regions which could account for some of the symptoms seen in schizophrenia. The hippocampus and the associated entorhinal cortex are important areas of the brain concerned in memory formation, information... 

The specificity of the process so far has been studied most extensively with the glutamate system using the technique of competition. As shown in Table I, a variety of substances diminish the rate of gluta-mate-C14 uptake when presented to the cells simultaneously with this amino acid. Glutamic-C12 acid served as a reference competitive substance. Glutamine is active and at very short incubation periods it sur-... 

The human clearly possesses a facial nerve amino acid system similar to the carnivore (16) and a petrosal system similar to the dog furaneol system (14, 17). The human also possesses a glutamate system, yet undetected in any experimental mammal (18, 19). 

The primates have been inadeguately studied, but those two with adequate single unit data suggest that the organization of primate taste systems is no simple matter. It is not obvious for instance, why the squirrel monkey may have an amino acid system like a carnivore and the macaque one like a rodent. The human taste system further complicates matters since man can best be viewed as a composite, having a sodium system like the rat and goat, carnivore acid and amino acid systems, a furaneol system like the dog and a glutamate system unlike any other mammal studied (14). 

The Glutamate System in Depression Quinolinic Acid as a Depressiogenic Substance... 

The Glutamate System in Schizophrenia Kynurenic Acid as a Schizophrenogenic Substance... 

---