Evaluation of the bronchodilator properties of Ro 31–6930, a novel potassium channel opener, in the guinea‐pig

Abstract

1 Ro 31–6930 (0.001-0.3 μm), cromakalim (0.03-3.0 μm), salbutamol (0.001-0.3 μm) and theophylline (0.3–100 μm) evoked dose-related reductions in guinea-pig spontaneous tracheal tone with IC₅₀ values of 0.044, 0.20, 0.021 and 21.0 μm respectively. All four agents also relaxed tone supported by betahistine, carbachol, 5-hydroxytryptamine (5-HT), leukotriene D₄ (LTD₄), U46619 and prostaglandin D₂ (PGD₂). 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.