Steric Aspects of Agonism and Antagonism at β‐Adrenoceptors: Experiments with the Enantiomers of Terbutaline and Pindolol

Abstract

The enantiomers of terbutaline, a β₂-selective adrenoceptor agonist, and pindolol, an unselective antagonist with partial agonist activity, were examined with respect to their ability to react in vitro on adrenoceptors in the trachea (mostly β₂) the soleus muscle (β₂) and in the papillary muscle of the left ventricle (β₁) from the guinea-pig. (+)-terbutaline was more than 3,000 times less potent than (—)-terbutaline in relaxing the trachea and in depressing subtetanic contractions of the soleus muscle. (+)-terbutaline did not inhibit the effects of (—)-terbutaline in these tissues. The effect of (—)-terbutaline on the papillary muscle was about 200 times weaker than on the soleus. (+)-terbutaline had a negligible inotropic effect on the papillary muscle and it did not inhibit the effect of isoprenaline. The enantiomers of pindolol did not show any consistent agonistic activity under the present experimental conditions. (—)-pindolol inhibited competetively the effect of isoprenaline to the same extent in all three tissues. (+)-pindolol was about 200 times less potent in this respect. Our data do not reveal any qualitative differences in the pharmacological properties between the optical isomers of terbutaline and pindolol, respectively.