AMPA receptor functional diversity Mixing and matching of subunits (see GABA receptors for examples) Further diversity generated by alternative splicing, editing Flip and flop splice forms desensitize at different rates, both have rapid onset kinetics (gluR2 homomers shown)
Metabotropic Glutamate Receptors (mGluR’s) mGluR function: modulatory Class C GPCR, very limited homology to rhodopsin mGluR’s are sub-divided based on sequence similarity Group I ( mGluR1 and mGluR5 )(Gq---PLC) Group II ( mGluR2 and mGluR3 )(Gi---AC) Group III ( mGluR4, mGluR6, mGluR7 and mGluR8 )(Gi---AC)
mGluR Ligands Glutamate binding site Allosteric Ligand binding site Competitive Ligand binding site
mGlu5 receptor antagonists exhibit the widest and most robust anxiolytic activity (MPEP (2-methyl-6-(phenylethynyl)-pyridine), a highly selective and brain-penetrant mGlu5 receptor antagonist) metabotropic glutamate receptor type 5 with the neuronal Ca2+-binding protein 2 modulates receptor function. activation of either mGlu(5) by positive allosteric modulators or stimulation of mGluR(2/3) receptors by agonists may offer new strategy in schizophrenia treatment.
mGlu7 receptor is prominently expressed in the basal ganglia, its role in restoring motor function in animal models of Parkinson's disease are being tried selective mGlu3 receptor agonists or enhancers are potential candidates as neuroprotective agents in Parkinson's disease, and their use might circumvent the limitations associated with the administration of exogenous GDNF.
Drugs Memantine-gating of blocked channels and binding to two sites on NMDA receptors PCP Ketamine Topiramate-inhibition of GluR5 kainate receptors could represent a key mechanism underlying the anticonvulsant activity of TPM Drugs in schizophrenia- Glutamate agonists or antagonists? Glycine agonists- d- cycloserine