Research Article | Volume: 6, Issue: 10, October, 2016

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

Soledad Alemán-Pantitlán César Millán-Pacheco Miguel A. Vázquez Fernando Hernández-Borja Rafael Villalobos-Molina Blanca Bazán-Perkins Samuel Estrada-Soto   

Open Access   

Published:  Oct 29, 2016

DOI: 10.7324/JAPS.2016.601004
Abstract

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.


Keyword:     Calcium channel blockadedocking studies Ethyl 6-amino-5-cyano-2-methyl-4-(pyridin-4-yl)-4H-pyran-3-carboxylaterelaxant effect tracheal relaxation.


Citation:

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.

Copyright:The Author(s). This is an open access article distributed under the Creative Commons Attribution Non-Commercial License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

HTML Full Text

Reference

Article Metrics

427 Absract views 26 PDF Downloads 453 Total views

   Abstract      Pdf Download

Related Search

By author names

Citiaion Alert By Google Scholar

Name Required
Email Required Invalid Email Address

Comment required