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Stereoselective features of (R)‐ and (S)‐atenolol: Clinical pharmacological, pharmacokinetic, and radioligand binding studies
Author(s) -
Stoschitzky Kurt,
Egginger Gabriele,
Zernig Gerald,
Klein Werner,
Lindner Wolfgang
Publication year - 1993
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.530050104
Subject(s) - atenolol , chemistry , enantiomer , radioligand , pharmacokinetics , pharmacology , stereoselectivity , heart rate , receptor , medicine , blood pressure , stereochemistry , biochemistry , catalysis
In a randomized, double‐blind, cross‐over study in 12 healthy volunteers, the effects of single oral doses of 100 mg rac‐atenolol were compared during exercise to those of equal amounts of the optically pure enantiomers, i.e., 50 mg (R)‐ and 50 mg (S)‐atenolol. The mean rate pressure product decreased with rac‐atenolol (−37%; P < 0.01) and half‐dosed (S)‐atenolol (−35%; P < 0.01) to the same extent, whereas (R)‐atenolol caused no effect. Radioligand binding studies in beta‐adrenergic receptors of the guinea pig heart yielded a eudismic ratio of 46 for (S)‐ to (R)‐atenolol. The mean AUCs, maximal plasma concentrations, and plasma half‐lives of the enantiomers were similar regardless of whether they were administered as optically pure enantiomers or as racemic mixture. On the other hand, the AUC of (R)‐atenolol was 1.08‐fold greater ( P < 0.01) than that of the (S)‐enantiomer. The reason for this finding remains unclear. We conclude that only (S)‐atenolol, but not (R)‐atenolol, contributes to the beta‐blocking effect of currently used rac‐atenolol since the same effect can be elicited with the (S)‐enantiomer alone. © 1993 Wiley‐Liss, Inc.