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 both 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 microM) inhibited responses of sensitized tracheal rings stimulated with OA in a concentration-dependent manner, with an IC50 of 10 microM. 3. IZP-94005 (10 microM) 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 micrograms 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 mg kg-1), with a similar protocol, also inhibited OA-induced responses in this model. 6. We therefore suggest that IZP-94005 is a good candidate for further investigation as a possible antiasthma agent.
Bramley
A M
AM
Inflazyme Pharmaceuticals Ltd, Vancouver, Canada.
Langlands
J M
JM
Jones
A K
AK
Burgoyne
D L
DL
Li
Y
Y
Andersen
R J
RJ
Salari
H
H
D000280:Administration, Inhalation; D000403:Airway Resistance / Q000187:drug effects; D000704:Analysis of Variance; D000818:Animals; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D016535:Bronchial Hyperreactivity / Q000139:chemically induced / Q000188:drug therapy*; D016084:Bronchoconstriction / Q000187:drug effects*; D002217:Carbachol / Q000494:pharmacology; D006168:Guinea Pigs; D006636:Histamine Release / Q000187:drug effects; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D017835:Nedocromil / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D010047:Ovalbumin / Q000008:administration & dosage; D010991:Plethysmography; D013261:Sterols / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D014132:Trachea / Q000187:drug effects
D018927:Anti-Asthmatic Agents; D013261:Sterols; D017835:Nedocromil; C091550:contignasterol; D002217:Carbachol; D010047:Ovalbumin