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Abstract

In vivo bronchodilator action of a novel K+ channel opener, KC 399, in the guinea pig.

J Imagawa, K Kamei, S Yoshida, I Sugo, T Koga and H Nabata
Journal of Pharmacology and Experimental Therapeutics April 1994, 269 (1) 1-6;
J Imagawa
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K Kamei
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S Yoshida
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I Sugo
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T Koga
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H Nabata
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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.

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Journal of Pharmacology and Experimental Therapeutics
Vol. 269, Issue 1
1 Apr 1994
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Abstract

In vivo bronchodilator action of a novel K+ channel opener, KC 399, in the guinea pig.

J Imagawa, K Kamei, S Yoshida, I Sugo, T Koga and H Nabata
Journal of Pharmacology and Experimental Therapeutics April 1, 1994, 269 (1) 1-6;

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Abstract

In vivo bronchodilator action of a novel K+ channel opener, KC 399, in the guinea pig.

J Imagawa, K Kamei, S Yoshida, I Sugo, T Koga and H Nabata
Journal of Pharmacology and Experimental Therapeutics April 1, 1994, 269 (1) 1-6;
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