Benzonatate, a long chain polyglycol derivative chemically related to procaine, is a peripherally-acting and oral antitussive [1]. The antitussive effect of benzonatate is achieved by inhibiting the pulmonary stretch receptors, and it is realized through reversible and concentration-dependent inhibition of voltage-gated sodium channels (including Nav1.7) [2]. Benzonatate has been used to prevent the initiation and propagation of action potentials in the nerves responsible for detecting and responding to irritants in the airways [3].
In vivo, Benzonatate was injected at the sciatic nerve of Sprague-Dawley rats at a dose of 0.3ml (12.4mM) for 4 days, which induced sensory and motor blockage and caused inflammation and myotoxicity[4].
References:
[1] Dicpinigaitis P V, Gayle Y E, Solomon G, et al. Inhibition of cough-reflex sensitivity by benzonatate and guaifenesin in acute viral cough[J]. Respiratory medicine, 2009, 103(6): 902-906.
[2] Evans M S, Maglinger G B, Fletcher A M, et al. Benzonatate inhibition of voltage-gated sodium currents[J]. Neuropharmacology, 2016, 101: 179-187.
[3] Foti Randazzese S, Toscano F, Gambadauro A, et al. Neuromodulators in acute and chronic cough in children: an update from the literature[J]. International Journal of Molecular Sciences, 2024, 25(20): 11229.
[4] McGuire A, Ostertag-Hill C A, Aizik G, et al. Benzonatate as a local anesthetic[J]. PLoS One, 2023, 18(4): e0284401.