Trials of the bronchodilator activity of the isoenzyme‐selective phosphodiesterase inhibitor AH 21‐132 in healthy volunteers during a methacholine challenge test.

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Abstract
1. An approximately steady‐state reduction of specific airway conductance was induced in normal human subjects by means of a methacholine individualized loading+maintenance dose regime. Tested against this background bronchoconstriction, the mixed type III/IV phosphodiesterase inhibitor AH 21‐132, ingested in doses up to 90 mg, had no detectable bronchodilator activity. 2. AH 21‐132, infused intravenously over 15 min, evoked short‐lived bronchodilatation at doses of 20 and 40 mg, without affecting blood pressure or heart rate. 3. AH 21‐132, mixed 1:18.5 by weight with sucrose, dissolved in saline, nebulized and inhaled in doses between 2 and 24 mg of AH 21‐132, produced dose‐dependent bronchodilation. The ED50 was estimated as 9.2 mg AH 21‐132. The peak relief of imposed bronchoconstriction was 80% and the apparent half‐time of removal of AH 21‐132 from its site of action was 25 min. 4. Inhaled, nebulized, hypertonic sucrose had a minor bronchodilator action. 5. AH 21‐132, by intravenous and inhaled routes of administration, provides relief of methacholine‐induced bronchoconstriction.