Benzonatate

Benzonatate (Benzononatine) is an orally active and non-narcotic peripheral antitussive agent. Benzonatate is a reversible voltage-gated Na⁺ channels inhibitor. Benzonatate dampens the activity of cough stretch receptors^[1][2]. In Vitro:Benzonatate mechanism of action is through its peripheral anesthetic dampening the activity of pulmonary stretch receptors located in respiratory passages, lungs, and pleura, which mediate the cough reflex). It also has similar activity on aortic baroreceptors, atrial and vagal receptors. Benzonatate has no inhibitory action in the respiratory center^[1].
In two murine cell lines, catecholamine A differentiated (CAD) cells, which express primarily Nav1.7, and N1E-115, which express primarily Nav1.3, Benzonatate strongly and reversibly inhibits voltage-gated Na+ channels. Benzonatate causes both tonic and phasic inhibition in CAD cells and N1E-115 cells^[2]. In Vivo:Mice are orally gavaged Benzonatate at 10, 30, 75, and 100 mg/kg/day for males and 5, 15, and 50 mg/kg/day for females. Rats are gavaged at 10, 30, and 90 mg/kg/day for males and 5, 15, and 50 mg/kg/day for females. Higher doses in males. In both species, Benzonatate is not detected in plasma because of rapid ester hydrolysis producing 4-(butylamino) benzoic acid (BBA) and methylated polyethylene glycol polymer. Benzonatate is not carcinogenic in rodent carcinogenicity^[1].