title: Selectivity of oxymetazoline for urethral pressure vs blood pressure in the anaesthetized female rabbit.
abstract: OBJECTIVE
  The aim of this study was to test alpha-adrenergic reference agonists for tissue selectivity in the urethra and to pharmacologically characterize the functional alpha-adrenoceptor type of the female rabbit urethra in vivo.
  
  
  METHODS
  The effect of alpha-adrenergic agonists and antagonists on the urethral pressure was compared with that on blood pressure and heart rate measured simultaneously in the anaesthetized female rabbit.
  
  
  RESULTS
  Oxymetazoline, NS-49, phenylephrine and phenylpropanolamine enhanced the urethral pressure in a dose-dependent manner. Phenylephrine and phenylpropanolamine also enhanced the blood pressure with significantly lower ED50 (dose that gives half of the maximal enhancing effect) values than for the urethral pressure. This was in contrast to oxymetazoline and NS-49. The ED50 values for oxymetazoline on urethral pressure, and systolic and diastolic blood pressure were 0.00067, 0.0030 and 0.0020 mg/kg, respectively. The ED50 values for NS-49 on urethral pressure, and systolic and diastolic blood pressure were 0.019, 0.21 and 0.18 mg/kg, respectively. Clonidine and UK 14,304 had no effect on urethral or blood pressure. The oxymetazoline-evoked increase in urethral pressure was inhibited by WB-4101 with an ID50 (dose that gives half of the inhibitory effect) significantly lower than that for rauwolscine.
  
  
  CONCLUSIONS
  The results suggest that in the female rabbit in vivo activation of alpha1-adrenoceptors increased the urethral pressure. Phenylephrine and phenylpropanolamine, in contrast to oxymetazoline and NS-49, selectively enhanced blood pressure as compared with urethral pressure. Provided that the present results also have validity in humans, it would seem possible to develop urethra-selective drugs for treatment of stress incontinence with few or no cardiovascular side-effects.
authors.affiliation: Department of Pharmacology, Pharmacia and Upjohn, Uppsala, Sweden.
authors.forename: A R
authors.initials: AR
authors.lastname: Modiri
authors.forename: M G
authors.initials: MG
authors.lastname: Fredrickson
authors.forename: P G
authors.initials: PG
authors.lastname: Gillberg
authors.forename: P
authors.initials: P
authors.lastname: Alberts
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000494:pharmacology* / Q000627:therapeutic use; D000758:Anesthesia; D000813:Anilides / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D010109:Oxymetazoline / Q000494:pharmacology / Q000627:therapeutic use; D010656:Phenylephrine / Q000494:pharmacology / Q000627:therapeutic use; D010665:Phenylpropanolamine / Q000494:pharmacology / Q000627:therapeutic use; D011817:Rabbits; D018340:Receptors, Adrenergic, alpha-1 / Q000187:drug effects / Q000502:physiology; D014521:Urethra / Q000187:drug effects* / Q000502:physiology; D014550:Urinary Incontinence, Stress / Q000188:drug therapy; D015016:Yohimbine / Q000627:therapeutic use
chemical_list: C092989:3'-(2-amino-1-hydroxyethyl)-4'-fluoromethanesulfonanilide; D000316:Adrenergic alpha-Agonists; D000813:Anilides; D018340:Receptors, Adrenergic, alpha-1; D010656:Phenylephrine; D015016:Yohimbine; D010665:Phenylpropanolamine; D010109:Oxymetazoline