Published:  Oct 29, 2016DOI: 10.7324/JAPS.2016.601004
This study aims to investigate the mechanism of relaxant action of Ethyl 6-amino-5-cyano-2-methyl-4-(pyridin- 4-yl)- 4H-pyran-3-carboxylate (1) in in silico study and ex vivo tracheal rat rings pre-contracted with carbachol (1 µM). Compound 1 was more active than theophylline [a phosphodiesterases (PDE’s) inhibitor] used as positive control. Moreover, pretreatment with 1 significantly shifted to the right the carbachol-induced contraction and did not allow to reach the maximum effect (p<0.001). In addition, compound 1 (96.30 µM) produces significant (100%) relaxant effect on the contraction induced by KCl (80mM), and the CaCl2-induced contraction was completely abolished by 1 as nifedipine does (a L-type calcium channel blocker), used as positive control (p<0.001). Meanwhile, in the presence of isoproterenol (a β-adrenergic agonist), propranolol (a β-adrenergic antagonist), and K+ channel blocker 2-AP the relaxant curve was significantly modified (p<0.05). Compound 1 was docked on an outer cavity located on the intracellular side of the human L-type calcium channel model and interacts in the following chains and residues: chain IP (G51, W52, T53, D54), IVP (R45, E50, A51, Q53, D54) and IS6 (W4, F7). In conclusion, ex vivo and in silico approaches suggest that compound 1 induces its relaxant effect mainly by calcium channel blockade, but other mechanisms like potassium channel and cAMP accumulation could be involved.
Alemán-Pantitlán S, Millán-Pacheco C, Vázquez MA, HernándezBorja F, Villalobos-Molina R, Bazán-Perkins B, Estrada-Soto S. Mechanism of Relaxant Action of Ethyl 6-Amino-5-Cyano-2- Methyl-4-(Pyridin-4-Yl)-4h-Pyran-3-Carboxylate Mainly Through Calcium Channel Blockade in Isolated Rat Trachea. J App Pharm Sci, 2016; 6 (10): 029-036.
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