title: Effects of benzylic hydroxyl substitution on the alpha-adrenoceptor blocking activity of tolazoline.
abstract: The R(-)- and S(+)-enantiomers of alpha-hydroxytolazoline, the benzylic hydroxy-substituted derivative of the alpha-adrenoceptor antagonist, tolazoline, were evaluated at alpha 1- and alpha 2-adrenoceptors in canine saphenous vein. Benzylic hydroxyl substitution of tolazoline in either the R(-) or S(+) configuration significantly decreased affinity at both alpha 1- and alpha 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 alpha 1- and alpha 2-adrenoceptors is tolazoline greater than S(+)-alpha-hydroxytolazoline = R(-)-alpha-hydroxytolazoline, which is different from that order predicted by the Easson-Stedman hypothesis (i.e., R(-) greater than S(+) = desoxy). The findings support our contention that phenethylamines and imidazolines interact differently with alpha-adrenoceptors.
authors.affiliation: Department of Pharmacology, Smith Kline and French Laboratories, King of Prussia, PA 19406.
authors.forename: R R
authors.initials: RR
authors.lastname: Ruffolo
authors.forename: A J
authors.initials: AJ
authors.lastname: Nichols
authors.forename: P N
authors.initials: PN
authors.lastname: Patil
authors.forename: A
authors.initials: A
authors.lastname: Hamada
authors.forename: M
authors.initials: M
authors.lastname: Clark
authors.forename: D D
authors.initials: DD
authors.lastname: Miller
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D004285:Dogs; D005260:Female; D008297:Male; D013237:Stereoisomerism; D014043:Tolazoline / Q000031:analogs & derivatives* / Q000494:pharmacology*
chemical_list: D000319:Adrenergic beta-Antagonists; C052897:alpha-hydroxymethyltolazoline; D014043:Tolazoline