Editors' ChoicePharmacology

Taking antidepressants to heart

Sci. Signal.  10 Mar 2015:
Vol. 8, Issue 367, pp. ec56
DOI: 10.1126/scisignal.aab0694

Drug repurposing—extending currently Food and Drug Administration (FDA)–approved drugs to treat additional diseases—has both economic and safety advantages over new drug development. The selective serotonin reuptake inhibitor (SSRI) paroxetine, which is used as an antidepressant, selectively inhibits G protein (heterotrimeric guanine nucleotide–binding protein)–coupled receptor kinase 2 (GRK2), a kinase thought to contribute to heart failure progression. Schumacher et al. report that paroxetine blocked or reversed heart damage after myocardial infarction in a mouse model. These cardiac effects were distinct from the SSRI activity of paroxetine and were further enhanced by the concurrent treatment with β-blockers, clinically used drugs that inhibit β-adrenergic receptor signaling. Thus, paroxetine may be useful for treating heart failure.

S. M. Schumacher, E. Gao, W. Zhu, X. Chen, J. K. Chuprun, A. M. Feldman, J. J. G. Tesmer, W. J. Koch, Paroxetine-mediated GRK2 inhibition reverses cardiac dysfunction and remodeling after myocardial infarction. Sci. Transl. Med. 7, 277ra31 (2015). [Abstract]