[Specific and nonspecific effects of beta receptor blockers: stereoselectively different properties exemplified by (R)- and (S)-propranolol]

Abstract

Beta adrenoceptor antagonists bind specifically to beta receptors in a reversible way, so they inhibit beta stimulating actions of beta mimetics such as epinephrine, norepinephrine, isoprenaline, etc. The effect of beta adrenoceptor antagonism depends on the extent of sympathetic activity and is most pronounced during work and stress. Most beta blockers are administered as racemic mixtures consisting of 50% of the (R)- and 50% of the (S)-enantiomer, but only one enantiomer (e.g. (S)-propranolol) exerts beta blocking activity in therapeutic doses while the other one (e.g. (R)-propranolol) does not. But there is also a number of non-beta blocking actions of beta adrenoceptor antagonists that show variable stereoselectivity. Propranolol is explored most extensively in this field: 1. Only (R)-propranolol inhibits the conversion of thyroxine to triiodothyronine. 2. Both (R)- and (S)-propranolol exert class 1 antiarrhythmic activity. 3. Both (R)- and (S)-propranolol decrease the intraocular pressure. In all these indications mentioned above, beta blockade as an unwanted effect could be avoided by administering optically pure (R)-propranolol instead of the racemic mixture. Stereoselectivity does not only influence the effects but also metabolism, protein-binding etc. of beta adrenoceptor antagonists. In fact, the (R)- and the (S)-enantiomer of a beta adrenoceptor antagonist are 2 substances with different pharmacodynamic and pharmacokinetic properties. Nevertheless, they are currently used as racemic mixtures in research as well as in therapy without being aware of stereoselective implications although there are nowadays methods available to separate and isolate the optically pure enantiomers of most beta adrenoceptor antagonists with high purity and on large scale at reasonable costs.