Summary
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 α1-adrenoceptors in rat aorta. The rank order of potencies of the compounds in this system was as follows: tolazoline > R(−)-hydroxytolazoline > S(+)-hydroxytolazoline. The efficacy of R(−)-hydroxytolazoline was higher than that of tolazoline, though its affinity for the receptor was less. The K B 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 α2-adrenoceptors were studied in field-stimulated myenteric plexus-longitudinal muscle of guinea-pig ileum. These substances were blockers at presynaptic α2-adrenoceptors. Based on K B values, the order of affinity in this system was as follows: tolazoline > S(+)isomer ≥ R(−)-isomer. β-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 × 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 failled to show any significant activity in rat atria. Thus, the β-adrenoceptor mediated action appears to be insignificant. Steric aspects of α-adrenoceptor mediated events are discussed.
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This investigation was, in part, supported by a grant from the United States Public Service, National Institutes of Health, GM 29358
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Sengupta, J.N., Hamada, A., Miller, D.D. et al. Interaction of enantiomers of hydroxy tolazoline with adrenoceptors. Naunyn-Schmiedeberg's Arch Pharmacol 335, 391–396 (1987). https://doi.org/10.1007/BF00165553
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DOI: https://doi.org/10.1007/BF00165553