KCS

Glutamate (L-glutamic acid), the major excitatory transmitter in the mammalian central nervous system (CNS), exerts its effects through both ionotropic and metabotropic glutamate receptors, thereby generating the fast excitatory synaptic responses at the majority of CNS synapses and involved in pathologies of many brain diseases. While ionotropic glutamate receptors are ligand-gated ion channels responsible for mediation of glutamate fast transmission, the metabotropic glutamate receptors (mGlus) belong to family C of the Gprotein- coupled receptors (GPCRs) and modulate the strength of synaptic transmission and they are divided into three groups with eight subtypes on the basis of their sequence homology, pharmacology, and signal transduction mechanism. Group 1 consists of the mGluR1 and mGluR5, which are predominantly identified in post-synapses in the brain region, including the hippocampus, cerebellum, thalamic nuclei, and spinal cord. Recently studies show that selective mGluR5 antagonists may play a role in the treatment of neuropathic pain and other brain diseases. In this study, we report the synthesis and biological evaluation of novel tetrahydrothieno[2,3-c]pyridine derivatives as mGluR5 antagonists for treatment of neuropathic pain.