Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

Differences in Mode of Action of Cochinchinenin A and B on Tetrodotoxin-Resistant Sodium Channels

Chen Su^1,2, Wu Shui-cai¹, Zeng Yi¹, Liu Xiang-ming²

¹College of Life Science and Bioengineering, Beijing University of Technology, Beijing, 100124; ²College of Biomedical Engineering, South-Central of University for Nationalities, Hubei, Wuhan, 430074, China.

For correspondence:- Liu Xiang-ming Email: liu.xiangming@263.net Tel:+8602767843892

Received: 13 August 2012 Accepted: 25 April 2013 Published: 12 June 2013

Citation: Su C, Shui-cai W, Yi Z, Xiang-ming L. Differences in Mode of Action of Cochinchinenin A and B on Tetrodotoxin-Resistant Sodium Channels. Trop J Pharm Res 2013; 12(3):385-391 doi: 10.4314/tjpr.v12i3.17

© 2013 The authors.
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Abstract

Purpose: To explore the mechanism of antagonistic interaction between cochinchinenin A and B in modulating tetrodotoxin-resistant (TTR-X) sodium currents.

Methods: The time variation of the effects induced by cochinchinenin A and B on the TTX-R sodium currents in dorsal root ganglion (DRG) neurons of rats were observed using whole-cell patch clamp technique. Based on pharmacological fundamental theory, the modes of action of cochinchinenin A and B on TTX-R channels were distinguished.

Results: The scatter diagram which reflected the time variation of inhibition effect on TTX-R sodium currents induced by cochinchinenin A fitted well with occupancy theory equation (goodness of fit test, p > 0.05), while that of cochinchinenin B fitted well with rate theory equation (p > 0.05). The rate constants for combination and dissociation between cochinchinenin A and TTX-R sodium channel were (198.7 ± 39.9) x 10^-3 and (41.1 ± 6.2) x 10^-3respectively; while corresponding values for combination and association between cochinchinenin B and TTX-R sodium channel were (99.9 ± 16.8) x 10^-3 and (5.3 ± 0.4) x 10^-3 respectively.

Conclusion: The main cause of the antagonistic interaction between cochinchinenin A and B may be attributed to the different modes of their action on TTX-R sodium channels.

Keywords: Cochinchinenin, Tetrodotoxin-resistant sodium channel, Antagonistic interaction, Occupancy theory, Rate theory