ArticleBritish journal of pharmacology2026
Therapeutic potential of small molecules that block receptor-induced Kv7/M-current suppression in neuroprotection, seizures, and pain.
Article in British journal of pharmacology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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6 authors.
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Abstract
background and purposeNeuronal Kv7 channels generate low voltage-gated potassium currents known as the M-current. The M-current is transiently suppressed by activation of Gq-coupled receptors, caused by a loss of an essential cofactor phosphatidylinositol 4,5-bisphosphate (PIP EXPERIMENTAL APPROACH: The Kv7 cytosolic pocket was used as a target site for in silico screening of 3D molecular libraries of clinically used compounds. Candidate compounds were functionally validated using patch-clamp recordings in CHO cells heterologously expressing Kv7 channels and human M KEY
resultsSeveral compounds reduced oxotremorine-M-induced Kv7.2 current suppression. Dabigatran etexilate, carvedilol, and nebivolol were selected as model compounds for further study. These compounds (1) attenuated M CONCLUSION AND IMPLICATIONS: A new class of Kv7 channel modulators reduce M-current suppression and are efficacious in several disease models. This mechanism provides a rationale for developing novel therapeutics targeting this cytosolic site.
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