Interaction of enantiomers of hydroxy tolazoline with adrenoceptors.

Adrenoceptor-mediated effects of the enantiomers of hydroxytolazoline and tolazoline (i.e., desoxy derivative) have been investigated in vitro. The enantiomers and tolazoline were partial agonists of postjunctional alpha 1-adrenoceptors in rat aorta. The rank order of potencies of the compounds in this system was as follows: tolazoline greater than R(-)-hydroxytolazoline greater than S(+)-hydroxytolazoline. The efficacy of R(-)-hydroxytolazoline was higher than that of tolazoline, though its affinity for the receptor was less. The KB values for prazosin against these agonists were nearly equal, which indicated that these imidazolines activate the same type of receptor in rat aorta. The S(+)-isomer, however, produced both a prazosin sensitive and resistant component of the response. The interactions of the derivatives with presynaptic alpha 2-adrenoceptors were studied in field-stimulated myenteric plexus-longitudinal muscle of guinea-pig ileum. These substances were blockers at presynaptic alpha 2-adrenoceptors. Based on KB values, the order of affinity in this system was as follows: tolazoline greater than S(+)-isomer greater than or equal to R(-)-isomer. beta-Adrenoceptor mediated activity was quantitated in guinea-pig and rat atria. R(-)-hydroxytolazoline lacked chronotropic effects either in guinea pig or rat atria. At 3 X 10(-4) M the isomer did not antagonize the effect of isoproterenol in the atria. On the other hand, S(+)-hydroxytolazoline produced a variable chronotropic effect in guinea-pig atria, but failed to show any significant activity in rat atria. Thus, the beta-adrenoceptor mediated action appears to be insignificant. Steric aspects of alpha-adrenoceptor mediated events are discussed.