Steric aspects of agonism and antagonism at beta-adrenoceptors: experiments with the enantiomers of clenbuterol

The enantiomers of clenbuterol, a beta 2-selective adrenoceptor agonist with partial agonistic activity, were examined with respect to their ability to react in vitro on adrenoceptors in the trachea (mostly beta 2), the soleus muscle (beta 2) and in the papillary muscle of the left ventricle (beta 1) from the guinea-pig. (-)-Clenbuterol relaxed the carbachol contracted trachea and depressed the subtetanic contractions of the soleus muscle in a concentration-dependent manner. (+)-Clenbuterol was at least 1,000 times less potent in this respect. Both isomers inhibited competitively the effect of isoprenaline on the trachea, the (-)-isomer being about 100 times more active than the (+)-isomer. None of the isomers showed any detectable positive inotropic effect on the papillary muscle but both inhibited competitively the response to isoprenaline. Also in this respect (-)-clenbuterol was more potent than (+)-clenbuterol. It is concluded that the beta 2-agonistic as well as the beta 1-antagonistic effect of clenbuterol resides in the (-)-isomer and that the (+)-isomer does not seem to contribute to the pharmacological effects displayed by racemic clenbuterol.