Synthesis of novel analogs of cabergoline: Improving cardiovascular safety by removing 5-HT_2B receptor agonism

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-HT_2B receptor agonists. We prepared analogs of cabergoline and have identified several that have limited or no agonism at the 5-HT_2B receptor.