Genetically engineered animal models have facilitated understanding of the effects of the mutations in the FMR1 gene that causes fragile X syndrome (FXS) on brain development and function. Studies with these animal models suggest that the symptoms of FXS reflect excessive protein synthesis downstream of mGluR5, a metabotropic glutamate receptor. Blocking this receptor with an antagonist could yield an effective drug treatment. This project will develop an existing lead compound, an mGluR5 antagonist, and advance it through the preclinical studies necessary to fulfill FDA requirements to open an Investigational New Drug application and perform initial testing in humans. These studies will test the hypothesis that mGluR5 antagonists can be effective treatments of FXS and other disorders of brain development, including autism.