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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Tachykinin NK2 receptors further characterized in the lung with nonpeptide receptor antagonists.

Two nonpeptide tackykinin NK2 receptor antagonists have now been described, SR 48968 and GR 159897. These drugs are highly specific and very potent antagonists with affinity (binding and in vitro study) for NK2 receptors in the subnanomolar range (pKi = 9-10), without intrinsic activity. They act preferentially on the human NK2A receptor subtype. These drugs exert potent and long-acting antagonism by both i.v. and oral administration. Their use has first confirmed the preponderant role of NK2 receptors in airway smooth muscle contraction, especially in human bronchi. A role for NK2 receptor stimulation has also been clearly demonstrated in bronchoconstriction induced by various agents known to induce the release of tachykinins (capsaicin, resiniferatoxin, citric acid, sodium metabisulfite diethyl ether, serotonin, and bradykinin), in allergen-induced airway constriction in the guinea pig sensitized to ovalbumin, and in hyperpnea-induced bronchoconstriction. Inhibition of neurokinin A mediated or capsaicin-mediated dyspnea by SR 48968 has also been demonstrated in the guinea pig. SR 48968 also is very efficient in inhibiting cough induced by citric acid or capsaicin. Finally, SR 48968 is able to abolish in guinea pigs in vivo the bronchial hyperreactivity induced after 24 or 48 h by a citric acid challenge or an ovalbumin challenge, respectively. Thus, nonpeptide, long-acting NK2 receptor antagonists can be regarded as suitable tools for investigations in humans. They may shortly allow a precise determination of the role of tachykinins in asthmatic patients.[1]


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