title: Recent progress in the synthesis and characterization of group II metabotropic glutamate receptor allosteric modulators.
abstract: Group II metabotropic glutamate (mGlu) receptors consist of the metabotropic glutamate 2 (mGlu(2)) and metabotropic glutamate 3 (mGlu(3)) receptor subtypes which modulate glutamate transmission by second messenger activation to negatively regulate the activity of adenylyl cyclase. Excessive accumulation of glutamate in the perisynaptic extracellular region triggers mGlu(2) and mGlu(3) receptors to inhibit further release of glutamate. There is growing evidence that the modulation of glutamatergic neurotransmission by small molecule modulators of Group II mGlu receptors has significant potential for the treatment of several neuropsychiatric and neurodegenerative diseases. This review provides an overview of recent progress on the synthesis and pharmacological characterization of positive and negative allosteric modulators of the Group II mGlu receptors.
authors.affiliation: Department of Pharmacology and Vanderbilt Center for Neuroscience Drug Discovery, Nashville, Tennessee 37232, USA.
authors.forename: Douglas J
authors.initials: DJ
authors.lastname: Sheffler
authors.forename: Anthony B
authors.initials: AB
authors.lastname: Pinkerton
authors.forename: Russell
authors.initials: R
authors.lastname: Dahl
authors.forename: Athina
authors.initials: A
authors.lastname: Markou
authors.forename: Nicholas D P
authors.initials: ND
authors.lastname: Cosford
mesh_terms: D000494:Allosteric Regulation / Q000187:drug effects / Q000502:physiology; D000596:Amino Acids / Q000138:chemical synthesis / Q000494:pharmacology; D000818:Animals; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000138:chemical synthesis / Q000494:pharmacology; D018698:Glutamic Acid / Q000138:chemical synthesis / Q000494:pharmacology; D006801:Humans; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists / Q000037:antagonists & inhibitors* / Q000502:physiology
chemical_list: D000596:Amino Acids; D019086:Bridged Bicyclo Compounds, Heterocyclic; C118218:LY 379268; D018094:Receptors, Metabotropic Glutamate; C108822:metabotropic glutamate receptor 2; C102718:metabotropic glutamate receptor 3; D018698:Glutamic Acid