Studies on the mechanism of action of omeprazole

Antitussive Drugs—Past, Present, and Future

“…Proton pump inhibitors, typified by omeprazole, can also inhibit Na + -K + ATPase and are somewhat selective for the neuronal isoforms of the sodium pump (Keeling et al, 1985;Iwata et al, 1988). As discussed above, the results of studies evaluating the antitussive effects of PPIs have been disappointing (Chang et al, , 2011Faruqi et al, 2011;Shaheen et al, 2011).…”

Regulation of cough by neuronal Na+–K+ ATPases

“…This has typically been attributed to disease modification in patients suspected of or diagnosed with gastroesophageal reflux disease. But the sulfenamide inhibitors of H + -K + ATPase proton pumps also inhibit the related Na + -K + ATPase sodium pumps [46,47]. Proton pump inhibitors also restore normal cough responsiveness in guinea pigs with cough hypersensitivity resulting from allergic inflammation [48].…”

“…Many of these isozyme selective inhibitors display selectivity for the neuronal isoforms of Na + -K + ATPase utilizing the a 3 subunit. Amongst these a 3 selective inhibitors, a common mode of action implicates an electrophilic and perhaps even covalent interaction with the sodium pump subunit analogous to the covalent interactions of proton pump inhibitors with H + -K + ATPase [46,47]. These actions are both prevented and reversed by the reducing agents dithiothreitol and glutathione.…”

“…In a primary culture of hippocampal neurons (cells expressing both a 1 and a 3 subunits), which have high intrinsic firing rates at baseline, the administration of an a 3 -selective dose of ouabain produced an accumulation of sodium which depolarized these cells, halting their spontaneous activity [64]. By Table 1 Drugs that inhibit Na + -K + ATPase and prevent or reduce coughing Rat brain, kidney 6 mM Human, guinea pig [39][40][41][42][43][44][45][46][47][48] inducing an intracellular accumulation of Na + by transient superfusion with K + -free buffer, the authors were then able to demonstrate that inhibition of a 3 resulted in a markedly impaired ability of cells to extrude sodium. This suggests that a 3 subunits are essential for reestablishing ionic gradients under conditions of high intracellular sodium.…”

Specificity of the Substituted Benzimidazole B 823-08: A Prodrug for Gastric Proton Pump Inhibition

“…the kidney, heart, colon, and biliary can aliculus. Since acid-activated intermediates from substituted benzimidazoles inhibit the Na'/K'-ATPase in vitro [Keeling et al, 1985], organ functions which critically de pend on this enzyme activity were also in vestigated. There is increasing information on the benzimidazole sulfoxides, whereas the effects of benzimidazole sulfides have not been extensively investigated so far.…”