EFFECTS OF IZP-94005 (CONTIGNASTEROL) ON ANTIGEN-INDUCED BRONCHIAL RESPONSIVENESS IN OVALBUMIN-SENSITIZED GUINEA-PIGS

1 We have investigated the novel naturally occurring marine compound, IZP-94005 (contignasterol), as a potential anti-asthma agent, using bo th in vivo and in vitro models of allergen-induced bronchoconstriction and airway smooth muscle contraction. 2 Tracheal rings from ovalbumin (OA)-sensitized guinea-pigs were treated with various concentrations of IZP-94005 for 20 min prior to challenge with ovalbumin. IZP-94005 ( 3-30 mu M) inhibited responses of sensitized tracheal rings stimulated with OA in a concentration-dependent manner, with an IC50 of 10 mu M. 3 IZP-94005 (10 mu M) had no effect on carbachol-induced contractions of sensitized guinea-pig tracheal rings, although it did inhibit hist amine-induced responses of OA sensitized guinea-pig tracheal rings. 4 The effects of IZP-94005 in vivo were examined using OA-sensitized gui nea-pigs which were tracheotomized under anaesthesia and placed in a b ody plethysmograph. Measurements of lung resistance and compliance wer e performed by isovolumetric analysis of volume and trans-pulmonary pr essure. 5 IZP-94005 (50 and 200 mu g kg(-1)), by inhalation 20 min Fri er to OA challenge caused significant inhibition of the increase in lu ng resistance induced by OA in sensitized guinea-pigs, compared to veh icle-treated animals. Nedocromil sodium (20 mg kg(-1)), with a similar protocol, also inhibited OA-induced responses in this model. 6 We the refore suggest that IZP-94005 is a good candidate for further investig ation as a possible antiasthma agent.