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Tolperisone: Evaluation of the Lidocaine‐Like Activity by Molecular Modeling
Author(s) -
Fels Gregor
Publication year - 1996
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/ardp.19963290402
Subject(s) - conformational isomerism , chemistry , lidocaine , molecule , stereochemistry , molecular model , hydrogen bond , molecular dynamics , computational chemistry , biology , organic chemistry , neuroscience
Tolperisone ( 1 ), a muscle relaxant with lidocaine‐like activity, was compared to lidocaine ( 2 ) by molecular modeling methods. Conformational search analysis has been employed to find the global minima of these compounds along with numerous low energy conformations from which specific conformers were extracted that show good superimposition of the structural features important for protein binding. Two additional compounds, mepi‐ ( 3 ) and bupivacaine ( 4 ), were included in the analysis to validate the method as these ligands show very close structural and pharmacological relationship to lidocaine ( 2 ) and are assumed to bind to an identical site. As a result we find conformers of all four ligands that have exactly the same position and orientation of the potential sites for hydrogen bonding with the rest of the molecule showing close comparison of the three‐dimensional geometry. Semiempirical calculations furthermore reveal good agreement of the electrostatic potentials of these conformations indicating similar interactions with a receptor. We conclude that tolperisone ( 1 ) and lidocaine ( 2 ) despite their chemical divergence can still attach to identical protein binding sites.