Pharmacological profiles of a novel alpha 1-adrenoceptor agonist, PNO-49B, at alpha 1-adrenoceptor subtypes

Naunyn Schmiedebergs Arch Pharmacol. 1995 Jan;351(1):2-9. doi: 10.1007/BF00169057.

Abstract

The effects of a newly synthesized compound, PNO-49B, (R)-(-)-3'-(2-amino-1-hydroxyethyl)-4'-fluoromethanesulfonanilide hydrochloride, on alpha 1-adrenoceptor subtypes were examined in various tissues in which the following distribution of alpha 1-adrenoceptor subtypes has been suggested: dog carotid artery (alpha 1B), dog mesenteric artery (alpha 1N), rabbit thoracic aorta (alpha 1B + alpha 1L), rat liver (alpha 1B), rat vas deferens (alpha 1A + alpha 1L), rat cerebral cortex (alpha 1A + alpha 1B) and rat thoracic aorta (controversial subtype). PNO-49B (0.1-100 microM) produced concentration-dependent contractions in dog mesenteric artery, rabbit thoracic aorta, rat thoracic aorta and rat vas deferens; and the maximal amplitudes of contraction were almost the same as or slightly less than those of noradrenaline. By contrast, the maximal response to PNO-49B in dog carotid artery was markedly smaller than the response to noradrenaline. In rabbit thoracic aorta, the contractile response to PNO-49B was not affected by inactivation of the alpha 1B subtype with chloroethylclonidine (CEC), although the response to noradrenaline was attenuated by that treatment. The dissociation constants (KA) of PNO-49B were not different among the rat thoracic aorta, dog carotid and mesenteric arteries and rabbit thoracic aorta (CEC-pretreated). The contractile responses to PNO-49B were inhibited competitively by prazosin, HV723 (alpha-ethyl-3,4,5-trimethoxy-alpha-(3-((2-(2-methoxyphenoxy)-ethyl)- amino(propyl)benzeneacetonitrile fumarate) and by WB4101 (2-(2,6-dimethoxyphenoxyethyl)-aminomethyl-1,4- benzodioxane).(ABSTRACT TRUNCATED AT 250 WORDS)

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic alpha-1 Receptor Agonists*
  • Anilides / pharmacology*
  • Animals
  • Dogs
  • Female
  • In Vitro Techniques
  • Male
  • Muscle Contraction / drug effects
  • Muscle, Smooth / drug effects
  • Muscle, Smooth, Vascular / drug effects
  • Norepinephrine / pharmacology
  • Rabbits
  • Radioligand Assay
  • Rats
  • Rats, Wistar
  • Receptors, Adrenergic, alpha-1 / classification

Substances

  • 3'-(2-amino-1-hydroxyethyl)-4'-fluoromethanesulfonanilide
  • Adrenergic alpha-1 Receptor Agonists
  • Anilides
  • Receptors, Adrenergic, alpha-1
  • Norepinephrine