Metabotropic Glutamate Receptors in the Control of Neuronal Activity and as Targets for Development of Anti-Epileptogenic Drugs

Feng   Ru   Tang; Henry   F.   Bradford; Eng-Ang      Ling

Abstract

The anticonvulsant and neuroprotective properties of agonist and antagonist of metabotropic glutamate receptors (mGluRs ) have been known for 15 years or so. However, it is not yet clear whether these agents, and allied compounds, can be considered as candidate drugs for eventual use in the clinic to control the development of epilepsy, (i.e. as anti- epileptogenics), or for the control of seizures themselves (i.e. as anticonvulsants). In fact, few studies have been designed to test for these properties by, for instance, administering these agents during the chronic stages of experimental epilepsy to determine whether a tendency to generate spontaneously recurrent seizures, which often appear by epileptogenesis, could be prevented or stopped. Even in the acute stages, there are substantial differences in experimental design between the published studies. Thus, there are large variations in such factors as timing, and the route of administration of candidate drugs, the age, or species and strain of experimental animal used, and the experimental epilepsy model employed. Such variations often make it difficult to accurately assess the anticonvulsant, neuroprotective and antiepileptogenic properties of each candidate drug across a wide range of studies. This paper, will review neuroanatomical, neurochemical, neuropharmacological studies of mGluRs in animal models and in patients with temporal lobe epilepsy, and summarize anticonvulsive and neuroprotective effects of their agonists and antagonists in different seizure and epilepsy models in order to give direction for the development of new generation antiepileptogenic and anticonvulsive drugs.

Keywords: Metabotropic glutamate receptors (mGluRs), agonists and antagonists, anticonvulsive, anti-epileptogenic, glutamate- induced epileptic discharges

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