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.