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Stereoselective Interactions between Local Anesthetics and Ion Channels
Author(s) -
Valenzuela Carmen,
Moreno Cristina,
Cruz Alicia,
Macías Álvaro,
Prieto Ángela,
González Teresa
Publication year - 2012
Publication title -
chirality
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.43
H-Index - 77
eISSN - 1520-636X
pISSN - 0899-0042
DOI - 10.1002/chir.22051
Subject(s) - chemistry , stereoselectivity , enantiomer , sodium channel , chirality (physics) , drug , ion channel , stereochemistry , stereospecificity , pharmacodynamics , racemic mixture , pharmacology , pharmacokinetics , combinatorial chemistry , receptor , sodium , biochemistry , organic chemistry , medicine , nambu–jona lasinio model , chiral symmetry breaking , physics , quantum mechanics , catalysis , quark
Local anesthetics are useful probes of ion channel function and structure. Stereoselective interactions are especially interesting because they can reveal three‐dimensional relationships between drugs and channels with otherwise identical biophysical and physicochemical properties. Furthermore, stereoselectivity suggests direct and specific receptor‐mediated action, and identification of such stereospecific interactions may have important clinical consequences. The fact that drug targets are able to discriminate between the enantiomers present in a racemic drug is the consequence of the ordered asymmetric macromolecular units that form living cells. However, almost 25% of the drugs used in the clinical practice are racemic mixtures, and their individual enantiomers frequently differ in both their pharmacodynamic and pharmacokinetic profiles. Moreover, their effects can be similar to or different from the pharmacological effect of the drug and may contribute to the undesired effects of the drug. In other cases, the pharmacological effects induced by the two enantiomers on the molecular target are opposite. In the present manuscript, we will review the stereoselective effects of bupivacaine‐like local anesthetics on cardiac sodium and potassium channels. Chirality 24:944–950, 2012 . © 2012 Wiley Periodicals, Inc.