The aim of this FOA issued by the National Institute of Neurological Disorders and Stroke (NINDS), the National Institute on Alcohol Abuse and Alcoholism (NIAAA), and the National Institute on Drug Abuse (NIDA) is to facilitate the discovery of new small molecule probes for investigating biological function in the nervous system by providing funding for advanced medicinal chemistry and the biological testing of compounds. Eligible Investigators will have identified probe candidates via screening of small molecule collections, using in vitro assays of biological activity developed to interrogate these collections, and be able to show that the structural features of these small molecules are related to their biological activity. Project proposals should nominate small molecule probe candidates from distinct structural series for the further, iterative design and testing of analogues in structure-activity relationship studies, using in vitro assays of biological function adapted to the medium throughput screening requirements of this work. These studies should have the goal of developing a small molecule probe possessing the attributes (eg: affinity, selectivity, activity) required for its use in future pharmacological studies proposed by the investigator. Applicants are strongly encouraged to utilize publicly available cheminformatic capabilities for the acquisition of compounds, and semi-custom synthesis of analogues, which is required of these studies.