RP 58802B, a long-acting beta 2-adrenoceptor agonist: assessment of antiasthma activity in the guinea-pig in vivo

Pulm Pharmacol. 1992 Sep;5(3):203-12. doi: 10.1016/0952-0600(92)90042-f.


We have examined the protective actions of RP 58802B, a novel beta 2-adrenoceptor agonist, administered by the inhaled and oral routes in the anaesthetized and conscious guinea-pig against bronchospasm induced by histamine or antigen (ovalbumin). We have also examined the effects of RP 58802B on airway reactivity and inflammatory cell infiltration in platelet-activating factor (PAF) (aerosol)-induced bronchial hyperreactivity and on PAF (tracheal instillation)-induced microvascular leakage in the guinea-pig. Nebulized RP 58802B produced a rapid onset and long lasting inhibition of histamine-induced bronchospasm in the anaesthetized guinea-pig (EC50 = 3.2 +/- 0.9 micrograms/ml; duration greater than 90 min). Given orally, RP 58802B (5 mg/kg, 60 min before challenge) produced a greater than three-fold shift to the right of the dose-response curve and depressed the maximum response to histamine by 39 +/- 11%. Increasing the concentration to 25 mg/kg had no futher effect. Similar protection was still seen 4 h after oral dosing. In conscious guinea-pigs, RP 58802B (5 or 25 mg/kg, p.o. 60 min before challenge) significantly attenuated antigen-induced dyspnoea with the time to severe dyspnoea increasing from 170 +/- 32 to 325 +/- 32 s at the higher dose of drug. RP 58802B (10 or 25 mg/kg, p.o. 60 min before exposure to PAF) prevented the development of bronchial hyperreactivity. Although PAF-induced bronchial hyperreactivity was not accompanied by an increase in the number of pulmonary eosinophils, RP 58802B (25 mg/kg p.o.) reduced the numbers of eosinophils recovered by lavage. RP 58802B (10 mg/kg p.o.) significantly inhibited PAF-induced microvascular leakage into guinea-pig lung. These data suggest that RP 58802B, in addition to being a potent and long acting bronchodilator, may have a prophylactic role in preventing bronchial hyperreactivity and in reducing plasma exudation into the lungs.

Publication types

  • Comparative Study

MeSH terms

  • Administration, Inhalation
  • Administration, Oral
  • Adrenergic beta-Agonists / pharmacology*
  • Albuterol / pharmacology
  • Anesthesia
  • Animals
  • Antigens / administration & dosage
  • Asthma / drug therapy*
  • Asthma / physiopathology
  • Benzimidazoles / pharmacology*
  • Bronchi / drug effects
  • Bronchi / metabolism
  • Bronchial Hyperreactivity / chemically induced
  • Bronchial Hyperreactivity / drug therapy
  • Bronchoalveolar Lavage Fluid / metabolism
  • Bronchoconstriction / drug effects
  • Bronchoconstriction / physiology
  • Dextrans / pharmacokinetics
  • Ethanolamines / pharmacology*
  • Fluorescein-5-isothiocyanate / pharmacokinetics
  • Guinea Pigs
  • Histamine / pharmacology
  • Male
  • Platelet Activating Factor / pharmacology
  • Time Factors
  • Trachea / drug effects
  • Trachea / metabolism


  • Adrenergic beta-Agonists
  • Antigens
  • Benzimidazoles
  • Dextrans
  • Ethanolamines
  • Platelet Activating Factor
  • fluorescein isothiocyanate dextran
  • Histamine
  • RP 58802B
  • Fluorescein-5-isothiocyanate
  • Albuterol