Inhibition by Ro 31-6930 of agonist and allergen induced bronchoconstriction in anaesthetised guinea-pigs and cats.
Ro 31-6930, a potent smooth muscle relaxant from the novel class of potassium channel openers, has been compared with BRL 38227, salmeterol and theophylline in a range of models of airway function. Ro 31-6930 relaxed isolated tracheal muscle from sensitised guinea-pigs which had been contracted by ovalbumin and was equipotent with salmeterol in inhibiting antigen-induced bronchospasm in anaesthetised, sensitised guinea-pigs. In both anaesthetised guinea-pig and cat, Ro 31-6930, BRL 38227 and theophylline were more potent against 5-HT evoked increases in lung resistance than they were on falls in dynamic compliance. Although salmeterol had equivalent activity on both parameters it is unlikely that the small difference seen with the other compounds reflect a preferential effect on large airways. In addition, Ro 31-6930 was an effective bronchodilator when given by inhalation to the anaesthetised guinea-pig. In view of the protective activity of Ro 31-6930 against antigen challenge in the sensitised guinea-pig and its potency in relation to other bronchodilators, it is considered that compounds which relax airway smooth muscle by the opening of plasmalemmal potassium channels may have a role in the treatment of asthma.
Paciorek
P M
PM
Department of Biology, Roche Products Limited, Welwyn Garden City, Hertfordshire, UK.
Burden
D T
DT
Gater
P R
PR
Hawthorne
Y M
YM
Spence
A M
AM
Taylor
J C
JC
Waterfall
J F
JF
D000336:Aerosols; D000403:Airway Resistance / Q000187:drug effects; D000485:Allergens / Q000276:immunology*; D000818:Animals; D001578:Benzopyrans / Q000008:administration & dosage / Q000494:pharmacology*; D016084:Bronchoconstriction / Q000187:drug effects*; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000494:pharmacology*; D002415:Cats; D005260:Female; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008170:Lung Compliance / Q000187:drug effects; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009129:Muscle Tonus / Q000187:drug effects; D011725:Pyridines / Q000008:administration & dosage / Q000494:pharmacology*; D012701:Serotonin / Q000494:pharmacology; D013045:Species Specificity; D014132:Trachea / Q000187:drug effects
D000336:Aerosols; D000485:Allergens; D001578:Benzopyrans; D001993:Bronchodilator Agents; D011725:Pyridines; C062764:Ro 31-6930; D012701:Serotonin