title: In vivo bronchodilator action of a novel K+ channel opener, KC 399, in the guinea pig.
abstract: We evaluated the in vivo bronchodilator effects of KC 399, a novel K+ channel opener. In anesthetized guinea pigs, i.v. administration of KC 399 (1-10 micrograms/kg), BRL38227 (lemakalim, 10-100 micrograms/kg) and salbutamol (0.3-3 microgram/kg) evoked a dose-related reduction in the histamine-induced bronchoconstriction. The dose of KC 399 producing a 50% inhibition of the bronchoconstriction induced by histamine was 2.6 (1.9-3.6) microgram/kg. In exerting this action, KC 399 was approximately 13 times more potent than BRL38227, but approximately 4 times less potent than salbutamol. The bronchodilator action of i.v. KC 399 (10 micrograms/kg) lasted for over 30 min, whereas that induced by either BRL38227 (100 micrograms/kg) or salbutamol (3 micrograms/kg) lasted less than 10 min. When given by inhalation, KC 399 (1-30 micrograms/ml) induced a more prolonged effect and was a more potent bronchodilator than BRL38227 (0.3-1 mg/ml) in the histamine-induced bronchoconstriction model. Inhaled KC 399 (30 and 100 micrograms/ml) also prevented the antigen-induced bronchoconstriction in sensitized guinea pigs under anesthetic. When given by the oral route, KC 399, BRL38227 and salbutamol protected conscious guinea pigs from asphyxic collapse in response to inhaled histamine, their effective doses being 0.03, 1 and 3 mg/kg, respectively. From these in vivo experimental results, we conclude that KC 399 is an orally active, potent and long lasting bronchodilator.
authors.affiliation: Fuji-gotemba Research Laboratories, Chugai Pharmaceutical Company, Limited, Japan.
authors.forename: J
authors.initials: J
authors.lastname: Imagawa
authors.forename: K
authors.initials: K
authors.lastname: Kamei
authors.forename: S
authors.initials: S
authors.lastname: Yoshida
authors.forename: I
authors.initials: I
authors.lastname: Sugo
authors.forename: T
authors.initials: T
authors.lastname: Koga
authors.forename: H
authors.initials: H
authors.lastname: Nabata
mesh_terms: D000280:Administration, Inhalation; D000420:Albuterol / Q000494:pharmacology; D000758:Anesthesia; D000818:Animals; D000941:Antigens / Q000494:pharmacology; D001249:Asthma / Q000188:drug therapy; D001578:Benzopyrans / Q000494:pharmacology*; D016084:Bronchoconstriction / Q000187:drug effects; D001993:Bronchodilator Agents / Q000494:pharmacology*; D003243:Consciousness; D019806:Cromakalim; D004195:Disease Models, Animal; D006168:Guinea Pigs; D006632:Histamine; D007114:Immunization; D007275:Injections, Intravenous; D008297:Male; D015221:Potassium Channels / Q000187:drug effects*; D011758:Pyrroles / Q000494:pharmacology
chemical_list: D000941:Antigens; D001578:Benzopyrans; D001993:Bronchodilator Agents; D015221:Potassium Channels; D011758:Pyrroles; D019806:Cromakalim; C085685:KC 399; D006632:Histamine; D000420:Albuterol