title: HCN Channels Modulators: The Need for Selectivity.
abstract: Hyperpolarization-activated, cyclic nucleotide-gated (HCN) channels, the molecular correlate of the hyperpolarization-activated current (If/Ih), are membrane proteins which play an important role in several physiological processes and various pathological conditions. In the Sino Atrial Node (SAN) HCN4 is the target of ivabradine, a bradycardic agent that is, at the moment, the only drug which specifically blocks If. Nevertheless, several other pharmacological agents have been shown to modulate HCN channels, a property that may contribute to their therapeutic activity and/or to their side effects. HCN channels are considered potential targets for developing drugs to treat several important pathologies, but a major issue in this field is the discovery of isoform-selective compounds, owing to the wide distribution of these proteins into the central and peripheral nervous systems, heart and other peripheral tissues. This survey is focused on the compounds that have been shown, or have been designed, to interact with HCN channels and on their binding sites, with the aim to summarize current knowledge and possibly to unveil useful information to design new potent and selective modulators.
authors.affiliation: University of Florence, Department of Neurosciences, Psychology, Drug Research and Child's Health, Section of Pharmaceutical and Nutraceutical Sciences, via Ugo Schiff 6, 50019 Sesto Fiorentino, Italy. novella.romanelli@unifi.it.
authors.forename: Maria
authors.initials: M
authors.lastname: Novella Romanelli
authors.forename: Laura
authors.initials: L
authors.lastname: Sartiani
authors.forename: Alessio
authors.initials: A
authors.lastname: Masi
authors.forename: Guido
authors.initials: G
authors.lastname: Mannaioni
authors.forename: Dina
authors.initials: D
authors.lastname: Manetti
authors.forename: Alessandro
authors.initials: A
authors.lastname: Mugelli
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Cerbai
mesh_terms: D000818:Animals; D015195:Drug Design; D006801:Humans; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels / Q000037:antagonists & inhibitors* / Q000378:metabolism; D049990:Membrane Transport Modulators / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure
chemical_list: D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D049990:Membrane Transport Modulators