Effects of IZP‐94005 (contignasterol) on antigen‐induced bronchial responsiveness in ovalbumin‐sensitized guinea‐pigs

Abstract

Canada1 We have investigated the novel naturally occurring marine compound, , as a potential anti-asthma agent, using both in vivo and in vitro models of allergen-induced bronchoconstriction and airway smooth muscle contraction. 3 IZP-94005 (10 gM) had no effect on carbachol-induced contractions of sensitized guinea-pig tracheal rings, although it did inhibit histamine-induced responses of OA sensitized guinea-pig tracheal rings. 4 The effects of IZP-94005 in vivo were examined using OA-sensitized guinea-pigs which were tracheotomized under anaesthesia and placed in a body plethysmograph. Measurements of lung resistance and compliance were performed by isovolumetric analysis of volume and trans-pulmonary pressure.5 IZP-94005 (50 and 200 pg kg-'), by inhalation 20 min prior to OA challenge caused significant inhibition of the increase in lung resistance induced by OA in sensitized guinea-pigs, compared to vehicle-treated animals. Nedocromil sodium (20 mg kg-'), with a similar protocol, also inhibited OAinduced responses in this model. 6 We therefore suggest that IZP-94005 is a good candidate for further investigation as a possible antiasthma agent.

The effects of contignasterol (IZP-94,005) on allergen-induced plasma protein exudation in the tracheobronchial airways of sensitized guinea - pigs in vivo

“…It inhibited allergen-induced contraction of trachea in vitro and protected the animals against bronchoconstriction produced by allergen in vivo [3]. It also attenuated allergen-induced eosinophil infiltration and activation in the lungs [4].…”

“…(i.e. superfused directly onto the tracheal mucosal surface) because, although contignasterol has been shown to be orally active [3,4], we were interested in its topical activity in the airways.…”

“…Seventy five male or female, randomly bred, English shorthair guinea pigs (100-250 g) were sensitized to ovalbumin using the regime of Bramley and coworkers [3]. Each animal received 100 mg ovalbumin i. p. and 100 mg ovalbumin i.m., followed 24 h later by a further injection of 50 mg ovalbumin i. m. The animals were used in an experiment 21 to 36 days later.…”

“…Pharmacological testing of contignasterol has shown that it can inhibit allergen-induced histamine release from rat mast cells [2] and from guinea-pig lung tissue in vitro [3]. It is at least as potent as nedocromil in inhibiting allergen-induced bronchoconstriction in sensitized guinea-pigs in vivo [3].…”

“…It is at least as potent as nedocromil in inhibiting allergen-induced bronchoconstriction in sensitized guinea-pigs in vivo [3]. It can also inhibit the infiltration, and activation, of eosinophils into airways in guinea-pigs [4] and rats [5].…”