Phenylpropanolamine constricts mouse and human blood vessels by preferentially activating α2-adrenoceptors

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Phenylpropanolamine (dl-norephedrine) was one of the most widely used therapeutic agents to act on the sympathetic nervous system. Because of concerns regarding incidents of stroke, its use as a nasal decongestant was discontinued. Although considered an α1-adrenergic agonist, the vascular adrenergic pharmacology of phenylpropanolamine was not fully characterized. Unlike most other circulations, the vasculature of the nasal mucosa is highly enriched with constrictor α2-adrenoceptors. Therefore, experiments were performed to determine whether phenylpropanolamine activates vascular α2-adrenoceptors. Mouse tail and mesenteric small arteries and human small dermal veins were isolated and analyzed in a perfusion myograph. The selective α1-adrenergic agonist phenylephrine caused constriction of tail and mesenteric arteries and human veins. The selective α2-adrenergic agonist UK14,304 [5-bromo-N-(4,5-dihydro-1H-imidazol-2-yl)-6-quinoxalinamine] caused constriction in tail arteries and in human veins, but not mesenteric arteries. The lack of constriction to UK14,304 was also observed in endothelium-denuded mesenteric arteries. Phenylpropanolamine constricted both types of artery but was 62-fold more potent in tail arteries. In mesenteric arteries, constriction to phenylpropanolamine was not affected by the selective α2- adrenergic antagonist, rauwolscine (10-7 M) but was abolished by the selective α1-adrenergic antagonist, prazosin (3 × 10 -7 M). In contrast, constriction to phenylpropanolamine in tail arteries and in human veins was inhibited by rauwolscine but not prazosin. Therefore, phenylpropanolamine is a preferential α2-adrenergic agonist. At low concentrations, it constricts blood vessels that express functional α2-adrenoceptors, whereas at much higher concentrations, phenylpropanolamine also activates vascular α1- adrenoceptors. This action likely contributed to phenylpropanolamine's therapeutic activity, namely constriction of the nasal vasculature.

Original languageEnglish (US)
Pages (from-to)432-439
Number of pages8
JournalJournal of Pharmacology and Experimental Therapeutics
Issue number1
StatePublished - Apr 2005
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology


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