There is mounting evidence to suggest that a treatment for Angelman syndrome is not just possible, but probable. The lack of known molecular targets associated with AS has hampered the development of specific therapeutics. However, a recent surge of potential therapeutics for other disorders associated with cognitive disruption has begun to be used in human clinical trials. The molecular modes of action for many of these new therapeutic agents have correlates to counter the molecular defects observed in AS. Thus, this proposal seeks to determine the effectiveness of compounds that are FDA approved and currently being used in clinical trials on the well-established AS mouse model. We propose to look at 4 of these compounds at the level of: 1) Degree of cognitive enhancement. 2) Rectification of a biological and genetic abnormality. 3) Increase in synaptic function and/or plasticity. It is our hope that these compounds will have a positive effect on one or more of these aspects. Furthermore, any positive results will prompt a full preclinical evaluation of the compound(s) and may lead to the development of an effective AS therapeutic.