Background: The Kv7 (KCNQ) subfamily of voltage-gated potassium channels
consists of 5 members (Kv7.1-5) each showing characteristic tissue distribution and
physiological roles. Given their functional heterogeneity, Kv7 channels represent important
pharmacological targets for the development of new drugs for neuronal, cardiovascular
and metabolic diseases.
Objective: In the present manuscript, we focus on describing the pharmacological relevance
and potential therapeutic applications of drugs acting on neuronally-expressed
Kv7.2/3 channels, placing particular emphasis on the different chemotypes, and highlighting
their pharmacodynamic and, whenever possible, pharmacokinetic peculiarities.
Methods: The present work is based on an in-depth search of the currently available scientific
literature, and on our own experience and knowledge in the field of neuronal Kv7
channel pharmacology. Space limitations impeded to describe the full pharmacological
potential of Kv7 channels; thus, we have chosen to focus on neuronal channels composed
of Kv7.2 and Kv7.3 subunits, and to mainly concentrate on their involvement in epilepsy.
Results: An astonishing heterogeneity in the molecular scaffolds exploitable to develop
Kv7.2/3 modulators is evident, with important structural/functional peculiarities of distinct
Conclusion: In the present work we have attempted to show the current status and growing
potential of the Kv7 pharmacology field. We anticipate a bright future for the field,
and express our hopes that the efforts herein reviewed will result in an improved treatment
of hyperexcitability (or any other) diseases.