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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Comparison of the effects of four Na+ channel analgesics on TTX-resistant Na+ currents in rat sensory neurons and recombinant Nav1.2 channels.

Na(+) channel blockers are highly effective analgesics. Among the neuronal Na(+) channel subtypes, Nav1.8 is discussed to be of importance for certain pain states, and Nav1.8-preferring Na(+) channel blockers should be able to relief pain without causing severe effects (due to the restricted expression of this channel type). In this study, the effects of four Na(+) channel blockers on rat tetrodotoxin-resistant (TTX-r) Na(+) channels (representing mostly Nav1.8) in sensory neurons were investigated using the patch-clamp technique in the voltage-clamp configuration, and compared with those on cells heterologously expressing Nav1.2 alpha subunits. The compounds were lidocaine, mexiletine, benzocaine, and ambroxol, which are clinically used to treat pain after local or systemic administration. The four compounds inhibited resting TTX-r channels concentration-dependently, with ambroxol being the most effective (IC(50) value: 34.3 microM), and benzocaine being the weakest (IC(50) value: 1,901 microM). All compounds shifted steady-state inactivation curves to more negative values. Ambroxol blocked resting TTX-r channels more potently than Nav1.2, the opposite was the case for lidocaine, mexiletine and benzocaine. Based on the drugs' potencies found in this study, and the published information on clinically achievable plasma levels, the amount of Na(+) channel block to induce analgesia after systemic administration was estimated.[1]


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