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Evaluation of the bronchodilator properties of Ro 31–6930, a novel potassium channel opener, in the guinea‐pig
Author(s) -
Paciorek P.M.,
Cowlrick I.S.,
Perkins R.S.,
Taylor J.C.,
Wilkinson G.F.,
Waterfall J. F.
Publication year - 1990
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1990.tb15797.x
Subject(s) - cromakalim , bronchoconstriction , salbutamol , bronchodilator , theophylline , leukotriene d4 , potassium channel opener , histamine , pharmacology , bronchodilatation , trachealis muscle , chemistry , anesthesia , medicine , potassium channel , leukotriene , agonist , asthma , receptor
1 Ro 31–6930 (0.001‐0.3 μ m ), cromakalim (0.03‐3.0 μ m ), salbutamol (0.001‐0.3 μ m ) and theophylline (0.3–100 μ m ) evoked dose‐related reductions in guinea‐pig spontaneous tracheal tone with IC 50 values of 0.044, 0.20, 0.021 and 21.0 μ m respectively. All four agents also relaxed tone supported by betahistine, carbachol, 5‐hydroxytryptamine (5‐HT), leukotriene D 4 (LTD 4 ), U46619 and prostaglandin D 2 (PGD 2 ). The order of potency of tracheal relaxants was always salbutamol > Ro 31–6930 > cromakalim > theophylline. 2 All four agents evoked dose‐related reductions in 5‐HT‐ and histamine‐induced bronchoconstriction in pithed vagotomised guinea‐pigs. The dose of Ro 31–6930 producing 50% inhibition of a 5‐HT bronchoconstriction was 11.6 μg kg −1 and the dose producing 50% inhibition of a histamine bronchoconstriction was 4.4 μg kg −1 . Salbutamol was approximately 4–5 times more potent than Ro 31–6930 whilst cromakalim was approximately 10 times less potent than Ro 31–6930 as a bronchodilator. Theophylline was markedly less potent than any of the other agents. 3 Ro 31–6930, cromakalim, salbutamol and theophylline each protected conscious guinea‐pigs from histamine‐induced respiratory distress. Ro 31–6930 and salbutamol were each effective at oral doses of 1.0 and 3.0 mg kg −1 whilst cromakalim was effective at oral doses of 3.0 and 10.0 mg kg −1 . Theophylline showed activity only at 300 mg kg −1 p.o. 4 Ro 31–6930 is a novel potassium channel opener which is a potent relaxant of guinea‐pig tracheal smooth muscle in vitro and a bronchodilator in vivo .