Lorcaserin (DB04871): A Comprehensive Monograph on a Selective 5-HT2C Agonist from Development to Market Withdrawal

Executive Summary

Lorcaserin, a small molecule drug identified by DrugBank ID DB04871, represented a significant development in the pharmacotherapy of obesity. Developed by Arena Pharmaceuticals and marketed under the brand names Belviq® and Belviq XR®, it was a selective serotonin 5-HT2C receptor agonist designed to promote satiety and reduce food intake.[1] Its approval by the U.S. Food and Drug Administration (FDA) in 2012 marked the end of a 13-year period without any new prescription anti-obesity medications, generating considerable anticipation within the medical community.[3]

The mechanism of action of Lorcaserin involves the activation of 5-HT2C receptors on pro-opiomelanocortin (POMC) neurons in the hypothalamus, a key pathway in appetite regulation.[5] Clinical efficacy, established in a series of Phase III trials, was considered modest; patients typically achieved a placebo-subtracted weight loss of approximately 3-4 kilograms over one year of treatment.[5] A critical component of its development and regulatory approval was its high selectivity for the 5-HT2C receptor over the 5-HT2B subtype, a feature intended to avoid the cardiac valvulopathy and pulmonary hypertension that led to the withdrawal of earlier, non-selective serotonergic agents like fenfluramine.[3]