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• W3212249613 endingPage "103" @default.
• W3212249613 startingPage "94" @default.
• W3212249613 abstract "Studies performed in healthy smokers have documented a diminished responsiveness to tussive challenges, and several lines of experimental evidence implicate nicotine as an antitussive component in both cigarette smoke and the vapors generated by electronic cigarettes (eCigs). We set out to identify the nicotinic receptor subtype involved in the antitussive actions of nicotine and to further evaluate the potential of nicotinic receptor-selective agonists as cough-suppressing therapeutics. We confirmed an antitussive effect of nicotine in guinea pigs. We additionally observed that the alpha-4 beta-2 (α4β2)-selective agonist Tc-6683 was without effect on evoked cough responses in guinea pigs, while the α7-selective agonist PHA 543613 dose-dependently inhibited evoked coughing. We subsequently describe the preclinical evidence in support of ATA-101, a potent and highly selective (α7) selective nicotinic receptor agonist, as a potential candidate for antitussive therapy in humans. ATA-101, formerly known as Tc-5619, was orally bioavailable and moderately central nervous system (CNS) penetrant and dose-dependently inhibited coughing in guinea pigs evoked by citric acid and bradykinin. Comparing the effects of airway targeted administration versus systemic dosing and the effects of repeated dosing at various times prior to tussive challenge, our data suggest that the antitussive actions of ATA-101 require continued engagement of α7 nicotinic receptors, likely in the CNS. Collectively, the data provide the preclinical rationale for α7 nicotinic receptor engagement as a novel therapeutic strategy for cough suppression. The data also suggest that α7 nicotinic acetylcholine receptor (nAChR) activation by nicotine may be permissive to nicotine delivery in a way that may promote addiction. SIGNIFICANCE STATEMENT: This study documents the antitussive actions of nicotine and identifies the α7 nicotinic receptor subtype as the target for nicotine during cough suppression described in humans. We additionally present evidence suggesting that ATA-101 and other α7 nicotinic receptor-selective agonists may be promising candidates for the treatment of chronic refractory cough." @default.
• W3212249613 created "2021-11-22" @default.
• W3212249613 creator A5007020825 @default.
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• W3212249613 date "2021-11-15" @default.
• W3212249613 modified "2023-10-12" @default.
• W3212249613 title "Evidence for Alpha₇ Nicotinic Receptor Activation During the Cough Suppressing Effects Induced by Nicotine and Identification of ATA-101 as a Potential Novel Therapy for the Treatment of Chronic Cough" @default.
• W3212249613 cites W1035229855 @default.
• W3212249613 cites W1493378518 @default.
• W3212249613 cites W1582014054 @default.
• W3212249613 cites W1793345278 @default.
• W3212249613 cites W1808500773 @default.
• W3212249613 cites W1962380667 @default.
• W3212249613 cites W1963597328 @default.
• W3212249613 cites W1971724892 @default.
• W3212249613 cites W1977201857 @default.
• W3212249613 cites W1977837017 @default.
• W3212249613 cites W1978262730 @default.
• W3212249613 cites W1981545113 @default.
• W3212249613 cites W1984236031 @default.
• W3212249613 cites W1984644694 @default.
• W3212249613 cites W1986240660 @default.
• W3212249613 cites W1988304143 @default.
• W3212249613 cites W1990736520 @default.
• W3212249613 cites W1991588393 @default.
• W3212249613 cites W1993337719 @default.
• W3212249613 cites W1999105253 @default.
• W3212249613 cites W2003333632 @default.
• W3212249613 cites W2003433756 @default.
• W3212249613 cites W2018355604 @default.
• W3212249613 cites W2020365161 @default.
• W3212249613 cites W2024557624 @default.
• W3212249613 cites W2024765705 @default.
• W3212249613 cites W2027859599 @default.
• W3212249613 cites W2029054224 @default.
• W3212249613 cites W2030075669 @default.
• W3212249613 cites W2031829706 @default.
• W3212249613 cites W2032605142 @default.
• W3212249613 cites W2034082268 @default.
• W3212249613 cites W2037079152 @default.
• W3212249613 cites W2049008523 @default.
• W3212249613 cites W2049486700 @default.
• W3212249613 cites W2049890645 @default.
• W3212249613 cites W2050246450 @default.
• W3212249613 cites W2060488758 @default.
• W3212249613 cites W2061549429 @default.
• W3212249613 cites W2064847368 @default.
• W3212249613 cites W2072012688 @default.
• W3212249613 cites W2078214218 @default.
• W3212249613 cites W2081327751 @default.
• W3212249613 cites W2087199848 @default.
• W3212249613 cites W2087228514 @default.
• W3212249613 cites W2087322817 @default.
• W3212249613 cites W2090059155 @default.
• W3212249613 cites W2092157736 @default.
• W3212249613 cites W2092727345 @default.
• W3212249613 cites W2094372233 @default.
• W3212249613 cites W2095859897 @default.
• W3212249613 cites W2096905212 @default.
• W3212249613 cites W2098098632 @default.
• W3212249613 cites W2108629233 @default.
• W3212249613 cites W2112893277 @default.
• W3212249613 cites W2115516581 @default.
• W3212249613 cites W2117389430 @default.
• W3212249613 cites W2128705526 @default.
• W3212249613 cites W2134885683 @default.
• W3212249613 cites W2141273252 @default.
• W3212249613 cites W2142431889 @default.
• W3212249613 cites W2147888401 @default.
• W3212249613 cites W2161593692 @default.
• W3212249613 cites W2162546185 @default.
• W3212249613 cites W2163270681 @default.
• W3212249613 cites W2163800681 @default.
• W3212249613 cites W2168457138 @default.
• W3212249613 cites W2168978656 @default.
• W3212249613 cites W2177689887 @default.
• W3212249613 cites W2227464669 @default.
• W3212249613 cites W2227501619 @default.
• W3212249613 cites W2263665616 @default.
• W3212249613 cites W2265979640 @default.
• W3212249613 cites W2301755841 @default.
• W3212249613 cites W2307842766 @default.
• W3212249613 cites W2319382238 @default.
• W3212249613 cites W2414191776 @default.
• W3212249613 cites W2417772297 @default.
• W3212249613 cites W2519142380 @default.
• W3212249613 cites W2548700507 @default.
• W3212249613 cites W2588418184 @default.
• W3212249613 cites W2596825811 @default.
• W3212249613 cites W2614739342 @default.
• W3212249613 cites W2752919082 @default.
• W3212249613 cites W2759322316 @default.

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