Effects of benzylic hydroxyl substitution on the α-adrenoceptor blocking activity of tolazoline

Abstract

The R(−)- and S(+)-enantiomers of α-hydroxytolazoline, the benzylic hydroxy-substiuted derivative of the α-adrenoceptor antagonist, tolazoline, were evaluated at α 1- and α 2-adrenoceptors in canine saphenous vein. Benzylic hydroxyl substitution of tolazoline in either the R(−) or S(+) configuration significantly decreased affinity at both α 1- and α 2-adrenoceptors. Differences in affinity between the R(−)- and S(+)-enantiomers were small, which is characteristic of imidazolines, but in marked contrast to phenethylamines where enantiomeric differences are large. The rank order of affinities at α 1- and α 2-adrenoceptors is tolazoline > S(+)- α-hydroxytolazoline = R(−)- α-hydroxytolazoline, which is different from that order predicted by the Easson-Stedman hypothesis (i.e., R(−) > S(+) = desoxy). The findings support our contention that phenethylamines and imidazolines interact differently with α-adrenoceptors.