Application of the Rotarod Assay in Drug Discovery Research

Drug development research is the process by which chemical compounds with inherent medicinal value are identified, screened, and eventually approved for human use by the Food and Drug Administration. Barring serendipitous findings, the research process begins with the identification of a clinical need that is currently not being met by the existing pharmacological market. More difficult is to connect the illness to a specific molecular target on which the candidate compound will act upon to produce the desired clinical effect. In vivo dosages have to be optimized to achieve the desired effect and toxic concentrations have to be known to determine the therapeutic window. Therefore, the Arnold Group is using a rotarod assay, which tests the motor coordination of Swiss Webster Mice at 10, 30, 60, 120, and 240 minutes after oral administration of new drug candidates. The purpose of such an assay is to identify motor impairment brought on by ingestion of a certain dose of a compound. The knowledge of the maximal tolerated dose is important for later toxicity studies that are carried out over a period of 14 days to enable FDA approval. The following data illustrates how the structure of a compound influences the effects on the motor coordination of Swiss Webster Mice