Mining the receptorome: A powerful approach for predicting efficacies and side effects of repositioned medications

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Bryan L. Roth, bryan_roth@med.unc.edu, National Institute of Mental Health Psychoactive Drug Screening Program and Department of Pharmacology, University of North Carolina at Chapel Hill, 8032 Burnett-Womack, CB # 7365, Chapel Hill, NC 27599
The in vitro pharmacological profiling of drugs using a large panel of cloned receptors, an approach that has come to be known as 'receptorome screening', has unveiled novel molecular mechanisms responsible for the actions and side effects of certain drugs. For instance, receptorome screening has been employed to uncover novel molecular targets involved in the actions of antipsychotic medications and the hallucinogenic mint extract salvinorin A. Receptorome screening has also implicated serotonin 5-hydroxy-t-ryptamine 2B receptors in the adverse cardiovascular effects of several medications and subsequent clinical studies have corroborated this prediction (see Roth NEJM, 2007). Receptorome screening represents one of the most effective methods for identifying potentially serious drug-related side effects at the preclinical stage, thereby avoiding significant economic and human health consequences. Receptorome screening also represents a powerful approach for rationally repositioning existing medications.

Supported by NIMH PDSP and Grants from NIMH and NIDA