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

Robert R. Ruffolo, Andrew J. Nichols, Popat N. Patil, Akihiko Hamada, Michael Clark, Duane Miller

Research output: Contribution to journalArticle

Abstract

The R(-)- and S(+)-enantiomers of α-hydroxytolazoline, the benzylic hydroxy-substiuted derivative of the α-adrenoceptor antagonist, tolazoline, were evaluated at α1- and α2-adrenoceptors in canine saphenous vein. Benzylic hydroxyl substitution of tolazoline in either the R(-) or S(+) configuration significantly decreased affinity at both α1- and α2-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 α1- and α2-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.

Original languageEnglish (US)
Pages (from-to)235-239
Number of pages5
JournalEuropean Journal of Pharmacology
Volume157
Issue number2-3
DOIs
StatePublished - Nov 22 1988
Externally publishedYes

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Tolazoline
Hydroxyl Radical
Adrenergic Receptors
Imidazolines
Phenethylamines
Saphenous Vein
Canidae

All Science Journal Classification (ASJC) codes

  • Cellular and Molecular Neuroscience
  • Pharmacology

Cite this

Effects of benzylic hydroxyl substitution on the α-adrenoceptor blocking activity of tolazoline. / Ruffolo, Robert R.; Nichols, Andrew J.; Patil, Popat N.; Hamada, Akihiko; Clark, Michael; Miller, Duane.

In: European Journal of Pharmacology, Vol. 157, No. 2-3, 22.11.1988, p. 235-239.

Research output: Contribution to journalArticle

Ruffolo, Robert R. ; Nichols, Andrew J. ; Patil, Popat N. ; Hamada, Akihiko ; Clark, Michael ; Miller, Duane. / Effects of benzylic hydroxyl substitution on the α-adrenoceptor blocking activity of tolazoline. In: European Journal of Pharmacology. 1988 ; Vol. 157, No. 2-3. pp. 235-239.
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