Synergistic protective effects with azelastine and salbutamol in a guinea pig asthma model.
Azelastine prevents down-regulation of beta 2-receptors and adenylate cyclase and upregulation of alpha 1-adrenoceptors induced by repeated allergen challenge in the guinea pig lung. In the present study the protective effects of azelastine and salbutamol and a combination of both drugs was investigated using aeroallergen-induced acute allergic bronchoconstrictor responses in conscious, actively sensitized guinea pig. The drugs were given orally 1 h prior to challenge. The oral PD50 was 230 micrograms/kg for azelastine and 1200 micrograms/kg for salbutamol. Both drugs showed a synergistic protective effect with a PD50 of 60 micrograms/kg of azelastine plus 120 micrograms/kg of salbutamol indicating a reduction in the PD50 of azelastine by a factor of 4 and of salbutamol by a factor of 10. These findings may explain the reduction in the use of salbutamol and theophylline with azelastine by chronic asthmatics.
Chand
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N
Wallace Laboratories, Cranbury, New Jersey, USA.
Achterrath-Tuckermann
U
U
Szelenyi
I
I
Sofia
R D
RD
D000284:Administration, Oral; D000420:Albuterol / Q000627:therapeutic use*; D000818:Animals; D001249:Asthma / Q000517:prevention & control*; D016535:Bronchial Hyperreactivity / Q000517:prevention & control; D001993:Bronchodilator Agents / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D006168:Guinea Pigs; D008297:Male; D010047:Ovalbumin; D010793:Phthalazines / Q000627:therapeutic use*
D001993:Bronchodilator Agents; D010793:Phthalazines; D010047:Ovalbumin; D000420:Albuterol; C020976:azelastine