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

Abstract

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.

• Authors: A M Bramley, J M Langlands, A K Jones, D L Burgoyne, Y Li, R J Andersen, H Salari
• Journal: British journal of pharmacology (Br J Pharmacol) Vol. 115 Issue 8 Pg. 1433-8 (Aug 1995) ISSN: 0007-1188 [Print] England
• PMID: 8564202 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Asthmatic Agents
• Sterols
• Nedocromil
• contignasterol
• Carbachol
• Ovalbumin

Topics

• Administration, Inhalation
• Airway Resistance (drug effects)
• Analysis of Variance
• Animals
• Anti-Asthmatic Agents (administration & dosage, pharmacology, therapeutic use)
• Bronchial Hyperreactivity (chemically induced, drug therapy)
• Bronchoconstriction (drug effects)
• Carbachol (pharmacology)
• Guinea Pigs
• Histamine Release (drug effects)
• Lung (drug effects, metabolism)
• Muscle Contraction (drug effects)
• Muscle, Smooth (drug effects)
• Nedocromil (administration & dosage, pharmacology, therapeutic use)
• Ovalbumin (administration & dosage)
• Plethysmography
• Sterols (administration & dosage, pharmacology, therapeutic use)
• Trachea (drug effects)