Searching for a new mGluRs positive allosteric modulators

Background: The metabotropic glutamate receptors play important neuromodulatory role throughout the brain. Intervention in glutamatergic neurotransmission through group III of mGluRs has been pursued for the treatment of many neurological and psychiatric disorders such as anxiety, schizophrenia, epilepsy, Parkinson disease, addiction. Aim: Identification of novel chemical scaffolds possessing group III of mGluRs positive allosteric modulation (PAM) activity. Methods: The screening study and activity of potential PAM was determined using forskolin-induced cAMP production, in HEK-293 T-REx cell lines stably expressing mGluRs (HTRF cAMP detection kit, Cisbio). Results: We have identified chemical scaffolds possessing mGluRs potential PAM activity. Those compounds alone and in the presence of L-Glutamine decreased the forskolin-induced cAMP production in HEK-293 T-REx mGluRs cells. Conclusions: It have been identified novel chemical scaffolds with mGluRs potential positive allosteric modulator activity. Acknowledgments This study is supported by project UDAPOIG.01.03.010-12-100/08-00 co-financed by European Union from the European Fund of Regional Development.