Interaction of enantiomers of hydroxy tolazoline with adrenoceptors

J. N. Sengupta, A. Hamada, Duane Miller, P. N. Patil

Research output: Contribution to journalArticle

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Abstract

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 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 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 KB 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.

Original languageEnglish (US)
Pages (from-to)391-396
Number of pages6
JournalNaunyn-Schmiedeberg's Archives of Pharmacology
Volume335
Issue number4
DOIs
StatePublished - Jan 1 1987
Externally publishedYes

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Tolazoline
Adrenergic Receptors
Guinea Pigs
Prazosin
Aorta
Imidazolines
Myenteric Plexus
Ileum
Isoproterenol
Muscles

All Science Journal Classification (ASJC) codes

  • Pharmacology

Cite this

Interaction of enantiomers of hydroxy tolazoline with adrenoceptors. / Sengupta, J. N.; Hamada, A.; Miller, Duane; Patil, P. N.

In: Naunyn-Schmiedeberg's Archives of Pharmacology, Vol. 335, No. 4, 01.01.1987, p. 391-396.

Research output: Contribution to journalArticle

Sengupta, J. N. ; Hamada, A. ; Miller, Duane ; Patil, P. N. / Interaction of enantiomers of hydroxy tolazoline with adrenoceptors. In: Naunyn-Schmiedeberg's Archives of Pharmacology. 1987 ; Vol. 335, No. 4. pp. 391-396.
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abstract = "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 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 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 KB 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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