Drug repurposing for cardiovascular diseases: new targets and indications for probenecid.

The available pharmacological options in the management of cardiovascular diseases such as ischemic heart disease and subsequent heart failure are effective in slowing the progression; however, the long-term prognosis is still poor raising the demand for new therapeutic strategies. Drug repurposing is a time- and cost-effective drug development strategy that offers approved and abandoned drugs a new chance at new indications. Recently, drugs used for the management of gout-related inflammation such as canakinumab or colchicine have been considered for drug repurposing in cardiovascular indications. The old uricosuric drug, probenecid has been identified as a novel therapeutic option in the management of specific cardiac diseases as well. Probenecid can modulate myocardial contractility and vascular tone as well as exerts anti-inflammatory properties. The mechanisms behind these beneficial effects might be related to purinergic-pannexin-1 signalling and transient receptor potential cation channel subfamily V member 2 (TRPV2) which are recently identified molecular targets of probenecid. In this review, we provide an overview on repurposing probenecid for ischemic heart disease and subsequent heart failure by summarizing the related experimental and clinical data and propose its potential repurposing to treat cardiovascular diseases.