Synthesis of novel analogs of cabergoline: improving cardiovascular safety by removing 5-HT2B receptor agonism

ACS Med Chem Lett. 2013 Feb 14;4(2):254-258. doi: 10.1021/ml3003814.


The dopamine agonist cabergoline has been used to treat prolactinomas, Parkinson's disease, Cushing's disease and sexual dysfunction. However, its clinical use was severely curtailed when it was found that patients taking cabergoline had an increased risk of developing cardiac-valve regurgitation. This potentially life-threatening condition has been associated with drugs, such as cabergoline, that are 5-HT2B receptor agonists. We prepared analogs of cabergoline and have identified several that have limited or no agonism at the 5-HT2B receptor.

Keywords: 5-HT2B; cabergoline; dopamine agonist; ergot alkaloid; sexual dysfunction.