Metabotropic glutamate receptor 5 antagonist, two-methyl-6-phenylethynyl-pyridine (MPEP), with low doses of MK801 and diazepam: A novel approach for controlling status epilepticus

Background and Objective: Status epilepticus (SE) is the most severe and feared form of epilepsy. The overall incidence of SE varies from 10 to 60 per 100,000 person-years, and the mortality is approximately 20% with 15 to 20% for adults and 3 to 15% for children. Chronic epilepsy often MTLE (20-40%), permanent neurologic defi cits (9 to 11%) and encephalopathy (6 to 15%) are probably caused by SE. Although many of current anti-status epilepticus drugs have been reported to be neuroprotective, this effect is not consistently with all these drugs and in all models of SE. Furthermore, most of these drugs targets on GABA A receptor, Na+, Ca++, K+ channels, not on glutamate and its receptors, the most common neurotransmitter and receptor in the central nervous system. This study aimed to assess anti-status epilepticus and neuroprotective effects of different antagonists of group I metabotropic glutamate receptor (mGluR) including mGluR1 and mGluR5. The pharmocokinetic profi le and longterm side effect of the promising candidate drug MPEP were also evaluated.