The HCN channel as a pharmacological target: Why, where, and how to block it

Year: 2021

Authors: Balducci V.; Credi C.; Sacconi L.; Romanelli M.N.; Sartiani L.; Cerbai E.

Autors Affiliation: Divisions of Pharmacology and Medicinal Chemistry, Department of Neuroscience, Psychology, Drug Sciences and Child Health (NeuroFarBa), University of Florence, Italy; National Institute of Optics (INO), National Research Council (CNR), Florence, Italy; European Laboratory for Non-Linear Spectroscopy (LENS), Florence, Italy

Abstract: Hyperpolarization-activated, cyclic nucleotide-gated (HCN) channels, expressed in a variety of cell types and in all tissues, control excitation and rhythm. Since their discovery in neurons and cardiac pacemaker cells, they attracted the attention of medicinal chemistry and pharmacology as novel targets to shape (patho)physiological mechanisms. To date, ivabradine represents the first-in-class drug as specific bradycardic agent in cardiac diseases; however, new applications are emerging in parallel with the demonstration of the involvement of different HCN isoforms in central and peripheral nervous system. Hence, the possibility to target specific isoforms represents an attractive development in this field; indeed, HCN1, HCN2 or HCN4 specific blockers have shown promising features in vitro and in vivo, with remarkable pharmacological differences likely depending on the diverse functional role and tissue distribution. Here, we show a recently developed compound with high potency as HCN2-HCN4 blocker; because of its unique profile, this compound may deserve further investigation.


Volume: 166      Pages from: 173  to: 181

More Information: This article was supported by a local grant from the University of Florence, by Ente Cassa di Risparmio di Firenze and by the Italian ministry of education, university and research (MIUR PRIN, 2017 grant RHYTHM-Insight to EC) .
KeyWords: HCN channels; Ivabradine; Isoform selectivity; Epilepsy; Neuropathic pain
DOI: 10.1016/j.pbiomolbio.2021.07.010

Citations: 7
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