Article date: August 1995
By: Andrew M. Bramley, John M. Langlands, Alana K. Jones, David L. Burgoyne, Ya Li, Raymond J. Andersen, Hassan Salari, in Volume 115, Issue 8, pages 1433-1438
We have investigated the novel naturally occurring marine compound, IZP‐94005 (contignasterol), as a potential anti‐asthma agent, using both in vivo and in vitro models of allergen‐induced bronchoconstriction and airway smooth muscle contraction.
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 μm) inhibited responses of sensitized tracheal rings stimulated with OA in a concentration‐dependent manner, with an IC50 of 10 μm.
IZP‐94005 (10 μm) 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.
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.
IZP‐94005 (50 and 200 μg kg−1), 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 μg kg−1), with a similar protocol, also inhibited OA‐ induced responses in this model.
We therefore suggest that IZP‐94005 is a good candidate for further investigation as a possible anti‐asthma agent.
We have investigated the novel naturally occurring marine compound, IZP‐94005 (contignasterol), as a potential anti‐asthma agent, using both in vivo and in vitro models of allergen‐induced bronchoconstriction and airway smooth muscle contraction.
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 μm) inhibited responses of sensitized tracheal rings stimulated with OA in a concentration‐dependent manner, with an IC50 of 10 μm.
IZP‐94005 (10 μm) 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.
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.
IZP‐94005 (50 and 200 μg kg−1), 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 μg kg−1), with a similar protocol, also inhibited OA‐ induced responses in this model.
We therefore suggest that IZP‐94005 is a good candidate for further investigation as a possible anti‐asthma agent.
DOI: 10.1111/j.1476-5381.1995.tb16634.x
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