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.