Benzonatate is a reversible voltage-gated sodium channel blocker.[1] It blocks Nav1.7 currents in a concentration- and voltage-dependent manner (IC50s = 5.9 and 1.4 μM at holding potentials of -100 and -70 mV, respectively) and inhibits action potential firing in catecholamine A differentiated (CAD) cells. Benzonatate also blocks 80% of Nav1.3 currents in N1E-115 cells when used at a concentration of 100 μM. In vivo, benzonatate (0.85 mg/min) reduces the frequency, but has no effect on the amplitude, of the cough reflex in anesthetized dogs.[2] Formulations containing benzonatate have been used as antitussive agents for the treatment of coughs.
Reference:
[1]. Evans, M.S., Maglinger, G.B., and Fletcher, A.M. Benzonatate inhibition of voltage-gated sodium currents. Neuropharmacology 101, 179-187 (2016).
[2]. Yanaura, S., Hosokawa, T., Kitagawa, H., et al. Effects of peripheral airway response on the cough reflex (author’s transl). Nihon Yakurigaku Zasshi. 76(8), 709-716 (1980).