Why the study?
The utility of 5-HT2B antagonists for treating conditions like PAH and VHD has been historically understudied due to clinical cardiotoxicity disasters associated with 5-HT2B agonists.
Highlights the potential of 5-HT2B antagonists as a therapeutic class for pulmonary arterial hypertension and valvular heart disease, shifting focus from the receptor's historical role as an antitarget.
The cardiotoxicity associated with des-ethyl-dexfenfluramine (norDF) and related agonists of the serotonin receptor 2B (5-HT2B) has solidified the receptor’s place as an “antitarget” in drug discovery. Conversely, a growing body of evidence has highlighted the utility of 5-HT2B antagonists for the treatment of pulmonary arterial hypertension (PAH), valvular heart disease (VHD), and related cardiopathies. In this Perspective, we summarize the link between the clinical failure of fenfluramine-phentermine (fen-phen) and the subsequent research on the role of 5-HT2B in disease progression, as well as the development of drug-like and receptor subtype-selective 5-HT2B antagonists. Such agents represent a promising class for the treatment of PAH and VHD, but their utility has been historically understudied due to the clinical disasters associated with 5-HT2B. Herein, it is our aim to examine the current state of 5-HT2B drug discovery, with an emphasis on the receptor’s role in the central nervous system (CNS) versus the periphery.
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Bender et al. (2023) conducted a review in Pulmonary arterial hypertension (PAH) and valvular heart disease (VHD). 5-HT2B antagonists was evaluated.
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