Enantiomers of bronchodilating β2-adrenoceptor agonists:: Is there a cause for concern?

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY

卷:103

Article

Waldeck, B

关键词: bronchodilator;    beta-adrenoceptor agonist;    asthma;    airway smooth muscle;    hyperreactivity;    enantiomer;    racemate;   

DOI  :  10.1016/S0091-6749(99)70414-8

来源: Elsevier

【 摘 要 】

All bronchodilating beta(2)-adrenoceptor agonists in current clinical use are derivatives of adrenaline and are available as racemates. Whereas the vast majority of the pharmacologic and clinical documentation has been made with the racemates, there are a few studies with the individual enantiomers, It thus appears that all established pharmacologic effects of racemic beta(2)-agonists reside in the (R)-enantiomer, with the (S)-enantiomer being virtually inactive. In recent years the suspicion has been raised that the (S)-enantiomer:of the beta(2)-agonists is responsible for induction of airway hyperreactivity,This suspicion is based primarily on results obtained in guinea pigs exposed to (S)-enantiomers of beta(2)-agonists, A number of experiments in vitro have been undertaken to find a mechanism of action for these observations in vivo. Most of the results obtained are equivocal. However, the observation that (S)-salbutamol may cause mobilization of intracellular Ca2+, apparently by means of a cholinergic mechanism, deserves further investigation. The clinical studies are focused on the enantiomers of salbutamol. They confirm the preclinical findings that the pulmonary, as well as the extrapulmonary, effects of salbutamol reside in the (R)-enantiomer. The studies available so far do not convincingly show clinically significant airway hyperreactivity after exposure to the (S)-enantiomer. Further studies are needed to settle this issue.

【 授权许可】

Free