TRIALS OF THE BRONCHODILATOR ACTIVITY OF THE ISOENZYME-SELECTIVE PHOSPHODIESTERASE INHIBITOR AH 21-132 IN HEALTHY-VOLUNTEERS DURING A METHACHOLINE CHALLENGE TEST

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 bronchodilatation. 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.