Abstract
We evaluated the effect of three new antileukotrienes (antiLT): 20076 (quinoline derivative) and 19354 (resacetophenone derivative) as LTB4 receptor inhibitor and 20556 (phenilethylamido-derivative) as a LTB4 and LTD4 receptor inhibitor on airway responsiveness of ovalbumin (OVA) sensitized Sprague-Dowley rats, divided in 5 groups: control, OVA-sensitized, treated with each antiLT. In vivo administration of antiLT in two doses of 10-2M/kg, at 12 h interval, was followed by bronchial challenge with OVA 0.2%. We analyzed the response of tracheal spirals in isolated organ bath, using an isometric transducer FORT 10 and a computerized BIOPAC MP100 system. The results revealed an increased basal tone after sensitization (0.21±0.12)x10-4N compared with controls (0.40±0.18)x10-4N (p<0.05), without significant improvement after antiLT administration. Contractile response to 10-5M acetylcholine (Ach) was strongly reduced after 20556 (0.49±0.08)x10-4N (p<0.01), followed by 19354 (0.61±0.15)x10-4N (p<0.05), compared with controls (0.94±0.24)x10-4N. Short term (5‘) preincubation with 10-5M antiLT showed no significant changes on Ach-induced contraction. We concluded that phenilethylamido-derivative is the most effective antiLT on both basal tone and contractile response of sensitized animals, due to its double action upon LTB4 and LTD4 receptors.