| Abstract: | ![]()
The metabotropic glutamate Group II receptors (mGlu2 and mGlu3 receptors) regulate the synaptic availability of glutamate and thus control the broad‐ranging neural transmission of glutamate as well as glutamate‐modulated transmission. The present review focuses on the potential role of Group II mGlu receptor antagonism in neurological and neuropsychiatric disorders. Recent findings have determined that agonists of metabotropic glutamate type 2/3 receptors (mGlu2/3) have antianxiety efficacy. Although it could be assumed that blockade of these receptors might engender anxiogenic responses, new data have indicted that these compounds produce antidepressant‐like, wake‐promoting, and pro‐cognitive effects in rodents. However, there are almost no data available to define the relative importance of mGlu2 versus mGlu3 receptors in these activities. Although there are some hints that antagonism of mGlu2/3 receptors could have additional therapeutic impact, the preponderance of data suggests that agonists of the mGlu2/3 receptors would be more likely to have efficacy in anxiety disorders, positive symptoms of schizophrenia, neurodegenerative disorders, and stroke, pain, and epilepsy. The pharmacology of antagonists of mGlu2/3 receptors suggests that such compounds could have a unique place in the medicinal arsenal for mood disorders as well as disorders of cognition and arousal. Given the activity surrounding the discovery of orally available antagonists for these receptors, there may be an opportunity for clinical investigation of these possibilities in the future. Drug Dev. Res. 67:757–769, 2006. © 2006 Wiley‐Liss, Inc. |
