Abstract
Novel central nervous system (CNS)-based therapies have been difficult to produce due to the complexity of the brain, limited knowledge of CNS-based disease development and associated pathways, difficulty in penetrating the blood brain barrier, and a lack of reliable biomarkers of disease. Reverse engineering in drug development allows the utilization of new knowledge of disease pathways and the use of innovative technology to develop medications with enhanced efficacy and reduced toxicities. Lorcaserin was developed as a specific 5HT2C serotonin receptor agonist for the treatment of obesity with limited off-target effects at the 5HT2A and 5HT2B receptors. This receptor specificity limited the hallucinogenic and cardiovascular side effects noted with other serotonin receptor agonists. Reverse engineering approaches to drug development reduce the cost of producing new medications, identify specific populations of patients that will derive the most benefit from therapy, and produce novel therapies with greater efficacy and limited toxicity.
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