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Updated: Jun 12, 2026

High-throughput Screening for Small-molecule Modulators of Inward Rectifier Potassium Channels
Published on: January 27, 2013
Hydroxylated analogs of mexiletine as tools for structural-requirements investigation of the sodium channel blocking
Alessia Catalano1, Alessia Carocci, Maria M Cavalluzzi
1Department of Medicinal Chemistry, University of Bari, Bari, Italy. a.catalano@farmchim.uniba.it
Abstract:
[2-(2-Aminopropoxy)-1,3-phenylene]dimethanol 1 and 4-(2-aminopropoxy)-3-(hydroxymethyl)-5-methylphenol 2, two dihydroxylated analogs of mexiletine - a well known class IB anti-arrhythmic drug - were synthesized and used as pharmacological tools to investigate the blocking-activity requirements of human skeletal muscle, voltage-gated sodium channel. The very low blocking activity shown by newly synthesized compounds corroborates the hypothesis that the presence of a phenolic group in the para-position to the aromatic moiety and/or benzylic hydroxyl groups on the aromatic moiety of local anesthetic-like drugs impairs either the transport to or the interaction with the binding site in the pore of Na(+) channels.
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