Effect of SN-408 (salmeterol hydroxynaphthoate) on passive cutaneous anaphylaxis and anaphylactic chemical mediator release in rats and guinea pigs

Abstract

The influence of SN-408 (salmeterol hydroxynaphthoate), a new selective beta 2-stimulant, on homologous passive cutaneous anaphylaxis (PCA), histamine- or serotonin-induced skin reaction and anaphylactic chemical mediator release was investigated in rats and guinea pigs, and its efficacy was compared with that of salbutamol, isoproterenol or disodium cromoglycate (DSCG). Intravenous administration of SN-408 (0.1-10 micrograms/kg) 1 min before, the antigen challenge dose-dependently inhibited rat homologous PCA to a similar extent to salbutamol. The inhibitory effect of these beta-agonists was quickly attenuated along with time between the administration of the drug and the antigen challenge. SN-408, however, still showed significant inhibition at the time of administration 5 min before the antigen challenge at which other agonists did not significantly affect any more. Ten micrograms/kg of SN-408 exhibited approximately 50% inhibition of skin reaction induced by either histamine or serotonin in rats. In addition, the compound represented concentration-dependent inhibition of the anaphylactic histamine release from the isolated rat peritoneal exudate cell, indicating that the inhibitory effect of SN-408 on rat homologous PCA is due to the suppression of mediator release in addition to the antagonism to mediator(s) released. The anaphylactic release of either histamine, immunoreactive (i-) leukotriene (LT)B4 or i-LTC4 from guinea pig lung fragments was concentration-dependently inhibited by 10(-10)-10(-7) g/ml SN-408, and the inhibitory potency appeared to be enhanced by prolongation of the pretreatment interval with the drug.(ABSTRACT TRUNCATED AT 250 WORDS)