positive allosteric modulators of type 5 metabotropic glutamate receptors (mglur5) and their therapeutic potential for the treatment of cns disorders积极的变构类型的调节器5 metabotropic谷氨酸受体(受体)和治疗中枢神经系统疾病的潜在治疗.pdfVIP

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positive allosteric modulators of type 5 metabotropic glutamate receptors (mglur5) and their therapeutic potential for the treatment of cns disorders积极的变构类型的调节器5 metabotropic谷氨酸受体(受体)和治疗中枢神经系统疾病的潜在治疗.pdf

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positive allosteric modulators of type 5 metabotropic glutamate receptors (mglur5) and their therapeutic potential for the treatment of cns disorders积极的变构类型的调节器5 metabotropic谷氨酸受体(受体)和治疗中枢神经系统疾病的潜在治疗

Molecules 2011, 16, 2097-2106; doi:10.3390/molecule OPEN ACCESS molecules ISSN 1420-3049 /journal/molecules Review Positive Allosteric Modulators of Type 5 Metabotropic Glutamate Receptors (mGluR5) and Their Therapeutic Potential for the Treatment of CNS Disorders Richard M. Cleva and M. Foster Olive * Department of Psychology, Arizona State University, Tempe, Arizona 85287, USA * Author to whom correspondence should be addressed; E-Mail: foster.olive@; Tel.: +1-480-727-9557. Received: 6 January 2011; in revised form: 8 February 2011 / Accepted: 28 February 2011 / Published: 2 March 2011 Abstract: Studies utilizing selective pharmacological antagonists or targeted gene deletion have demonstrated that type 5 metabotropic glutamate receptors (mGluR5) are critical mediators and potential therapeutic targets for the treatment of numerous disorders of the central nervous system (CNS), including depression, anxiety, drug addiction, chronic pain, Fragile X syndrome, Parkinson’s disease, and gastroesophageal reflux disease. However, in recent years, the development of positive allosteric modulators (PAMs) of the mGluR5 receptor have revealed that allosteric activation of this receptor may also be of potential therapeutic benefit for the treatment of other CNS disorders, including schizophrenia, cognitive deficits associated with chronic drug use, and deficits in extinction learning. Here we summarize the discovery and characterization of various mGluR5 PAMs, with an