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Review

How to Replace the Lost keys? Strategies Toward Safer KV7 Channel Openers

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Pages 337-355 | Received 26 Jul 2018, Accepted 30 Nov 2018, Published online: 25 Feb 2019
 

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.

Acknowledgments

was generated by L Schulig.

Financial & competing interests disclosure

A Link is the recipient of a grant by the Deutsche Forschungsgemeinschaft DFG (LI 765/7-1). C Bock is funded by this grant. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

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