How to replace the lost keys? Strategies toward safer KV 7 channel openers

Future Medicinal Chemistry
Christian Bock, Andreas Link

Abstract

The highly structurally similar drugs flupirtine and retigabine have been regarded as safe and effective for many years but lately they turned out to exert intolerable side effects. While the twin molecules share the mode of action, both stabilize the open state of voltage-gated potassium channels, the form and severity of adverse effects is different. The analgesic flupirtine caused drug-induced liver injury in rare but fatal cases, whereas prolonged use of the antiepileptic retigabine led to blue tissue discoloration. Because the adverse effects seem unrelated to the mode of action, it is likely, that both drugs that occupied important therapeutic niches, could be replaced. Reasons for the clinically relevant toxicity will be clarified and future substitutes for these drugs presented in this review.

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Citations

Apr 17, 2019·Organic & Biomolecular Chemistry·Abdrrahman S SururAndreas Link
Oct 22, 2019·Assay and Drug Development Technologies·Benjamin WilenkinBirgit T Priest
May 1, 2021·Journal of Medicinal Chemistry·Yang-Ming ZhangFa-Jun Nan
May 29, 2021·RSC Medicinal Chemistry·Matteo BorginiPeter Wipf

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Methods Mentioned

BETA
gene modification
biopsy
pharmacotherapy

Clinical Trials Mentioned

NCT02149836
NCT03043560
NCT02450552

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