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2B Determined: The Future of the Serotonin Receptor 2B in Drug Discovery.
J Med Chem
August 2023
Department of Biomedical Engineering, Vanderbilt University, Nashville, Tennessee 37240, United States.
The cardiotoxicity associated with -ethyl-dexfenfluramine (norDF) and related agonists of the serotonin receptor 2B (5-HT) has solidified the receptor's place as an "antitarget" in drug discovery. Conversely, a growing body of evidence has highlighted the utility of 5-HT 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-HT in disease progression, as well as the development of drug-like and receptor subtype-selective 5-HT antagonists.
View Article and Find Full Text PDFIdentifying new drugs associated with pulmonary arterial hypertension: A WHO pharmacovigilance database disproportionality analysis.
Br J Clin Pharmacol
December 2022
Pharmacovigilance Unit, Grenoble Alpes University Hospital, Grenoble, France.
Unlabelled: Since the 1960s, several drugs have been linked to the onset or aggravation of pulmonary arterial hypertension (PAH): dasatinib, some amphetamine-like appetite suppressants (aminorex, fenfluramine, dexfenfluramine, benfluorex) and recreational drugs (methamphetamine). Moreover, in numerous cases, the implication of other drugs with PAH have been suggested, but the precise identification of iatrogenic aetiologies of PAH is challenging given the scarcity of this disease and the potential long latency period between drug intake and PAH onset. In this context, we used the World Health Organization's pharmacovigilance database, VigiBase, to generate new hypotheses about drug associated PAH.
View Article and Find Full Text PDFInterventions for preventing weight gain after smoking cessation.
Cochrane Database Syst Rev
October 2021
Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK.
Background: Most people who stop smoking gain weight. This can discourage some people from making a quit attempt and risks offsetting some, but not all, of the health advantages of quitting. Interventions to prevent weight gain could improve health outcomes, but there is a concern that they may undermine quitting.
View Article and Find Full Text PDFFenfluramine repurposing from weight loss to epilepsy: What we do and do not know.
Pharmacol Ther
October 2021
Division of Clinical and Experimental Pharmacology, Department of Internal Medicine and Therapeutics, University of Pavia, Pavia, Italy.
In 2020, racemic-fenfluramine was approved in the U.S. and Europe for the treatment of seizures associated with Dravet syndrome, through a restricted/controlled access program aimed at minimizing safety risks.
View Article and Find Full Text PDFPharmacological and non-pharmacological strategies for obese women with subfertility.
Cochrane Database Syst Rev
March 2021
Social Determinants of Health Research Center, Yasuj University of Medical Sciences, Yasuj, Iran.
Background: Clinicians primarily recommend weight loss for obese women seeking pregnancy. The effectiveness of interventions aimed at weight loss in obese women with subfertility is unclear.
Objectives: To assess the effectiveness and safety of pharmacological and non-pharmacological strategies compared with each other, placebo, or no treatment for achieving weight loss in obese women with subfertility.
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