144,145 We discovered that the prototypic mGluR5 antagonist 6-methyl-2-(phenylethynyl) pyridine (MPEP), and GRN-529. a more selective negative allosteric modulators of the mGluRS receptor, reduced the high levels of repetitive check details self-grooming in BTBR mice,79,146 an inbred

strain that displays robust social deficits, low vocalizations in social settings, and high repetitive self-grooming and digging.42,58,60,65,78,79,147,148 In addition, GRN-529 reduced the high levels of stereotyped jumping that characterize another inbred strain, C58/I80,146,149 Further, MPEP reduced marble burying Inhibitors,research,lifescience,medical in Fmr1 knockout mice, reduced stereotypies in Swiss-Webster mice, and reduced repetitive self-grooming and marble burying in mice pretreated prenatally with valproic acid.14,150,151 These reports lend credence to the Inhibitors,research,lifescience,medical notion that interventions acting through mGluR5 receptors could confer specific benefits for treating repetitive behaviors, a major component

of the third diagnostic symptom of autism. Conclusions Promising early findings of therapeutic rescues in mouse models have energized the rational search for pharmacological treatments of autism spectrum disorder. While the optimal Inhibitors,research,lifescience,medical developmental period for pharmacological intervention remains to be determined, adults with autism will likely be recruited for the first clinical trials,152 since the risks of adverse drug reactions are predicted to be greater in children. Challenges will include Inhibitors,research,lifescience,medical discovering the critical window during development and/or adulthood at which interventions are useful, dosages, and treatment regimens which minimize toxicity. We have taken the first step in a long journey. Acknowledgments We thank Dr Mu Yang for Figures 1a and 3a, and Dr Jennifer Brielmaier for Figure 1b. Dr Yang was a Research Fellow and Dr Brielmaier was a Postdoctoral Fellow in the author’s Laboratory of Behavioral Neuroscience,

National Institute of Mental Health Intramural Research Program, Bethesda, MD.
Autistic disorder (autism), Asperger’s Inhibitors,research,lifescience,medical disorder, and pervasive developmental disorder not otherwise specified (PDD-NOS) are diagnostic subtypes of Pervasive Developmental Disorders Cytidine deaminase (PDDs) in the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision (DSM-IV-TR). In this review, these three diagnostic subtypes will collectively be referred to as “autism spectrum disorders” (ASDs), given the widespread use of this terminology in the recent literature. The following is a comprehensive review of available pharmacotherapies for the behavioral symptoms associated with ASDs in children, adolescents, and adults. Autism, as defined in DSM-IV-TR, is characterized by impaired reciprocal social interaction, aberrant language development or communication skills, and the presence of repetitive, stereotyped behavior, interests, or activities.