The ability of salbutamol and theophylline to suppress immediate allergic conjunctivitis in the guinea pig.
Topically administered salbutamol was extremely effective in suppressing immediate allergic conjunctivitis in the guinea pig; a dose as low as 0.1% elicited 98% inhibition. Topical pretreatment with 1% propranolol completely blocked the suppressant action of 0.1% salbutamol. This was also the case after systemic propranolol (1 mg/kg SC); the beta-adrenoceptor antagonist itself has no effect on antigen-induced inflammation. The effect of 0.1% salbutamol was unaltered by pretreatment with the specific beta 1-adrenoceptor antagonist betaxolol (1 mg/kg SC). In marked contrast, the suppressant action of 0.1% salbutamol was profoundly inhibited by pretreatment with the selective beta 2-adrenoceptor antagonist ICI-118,551 (0.5 mg/kg SC). The experiments employing beta-adrenoceptor antagonists unequivocally demonstrate that the salbutamol suppression of immediate allergic conjunctivitis in the guinea pig is mediated via the activation of beta 2-adrenoceptors. The methylxanthine phosphodiesterase inhibitor theophylline was active after oral administration, 50 mg/kg eliciting an 80% inhibition. Theophylline was inactive topically at 1% and 5%, but this could be due to the fact that the compound was insoluble at these concentrations. Thus, procedures that elevate cyclic-AMP levels suppress immediate hypersensitivity reactions in the guinea pig conjunctiva. Whether or nor this offers an alternative approach to treat allergic conjunctivitis in humans remains to be determined.
Gautheron
P
P
Centre de Recherche, Merck Sharp & Dohme-Chibret, Riom, France.
Sugrue
M F
MF
D000284:Administration, Oral; D000287:Administration, Topical; D000420:Albuterol / Q000037:antagonists & inhibitors / Q000627:therapeutic use*; D000818:Animals; D003233:Conjunctivitis, Allergic / Q000517:prevention & control*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006168:Guinea Pigs; D011433:Propranolol / Q000494:pharmacology; D013806:Theophylline / Q000627:therapeutic use*
D011433:Propranolol; D013806:Theophylline; D000420:Albuterol