Cough model

This cough model was used to determine SARs ofNTI derivatives. In addition to the antitussive efficacy of compounds, it is possible to assess not only compounds intrinsic affinity for the receptor but their absorption, distribution, metabolism, and excretion (ADME) properties. 

McKemy DD, Neuhausser WM, Julius D (2002) Identification of a cold receptor reveals a general role for TRP channels in thermosensation. Nature 416 52-58 McLeod RL, Bolser DC, Jia Y, Parra LE, Mutter JC, Wang X, Tulshian DB, Egan RW, Hey JA (2002) Antitussive effect of nociceptin/orphanin FQ in experimental cough models. Pulm Pharmacol Ther 15 213-216... 

Despite being used as a component in cough remedies since the introduction of a VapoRub in 1890, there are few human trials of menthol used alone as being effective. In a citric acid-induced cough model in healthy subjects. Packman and London (1980) found that menthol was effective, although 1,8-cineole was more ef cacious. The use of an aromatic unction rather than direct inhalation may have affected the results, since the inhalation of menthol has been shown in animal models to be signi cantly more effective at cough frequency reduction (28% and 56% at 10 and 30 pg/L, respectively) when compared to 1,8-cineole (Laude et al., 1994). 

The antitussive activity of the aqueous and alkaloid extracts from the roots of S. tuberosa, and five isolated stenine-type alkaloids neostenine, also named isostenine (3), tuberostemonine J (6), tuberostemonine H (7), pi-bisdehydroneotuberostemonine J (12) and neotuberostemonine (13), were evaluated in a guinea pig cough model. The alkaloid extract showed much more potent activity than the aqueous extract, indicating that the Stemona alkaloids are responsible for the antitussive activity of S. tuberosa. Neotuberostemonine (13) was the most active alkaloid, followed by neostenine, also named isostenine (3), tuberostemonine H (7), and tuberostemonine J (6) (2). 

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