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 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.
Foster
R W
RW
Department of Physiological Sciences, Medical School, University of Manchester, UK.
Rakshi
K
K
Carpenter
J R
JR
Small
R C
RC
D000280:Administration, Inhalation; D000284:Administration, Oral; D000328:Adult; D001980:Bronchi / Q000187:drug effects; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004333:Drug Administration Routes; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D016210:Methacholine Chloride / Q000494:pharmacology; D008875:Middle Aged; D009287:Naphthyridines / Q000008:administration & dosage / Q000494:pharmacology*; D010726:Phosphodiesterase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D013395:Sucrose / Q000494:pharmacology
D001993:Bronchodilator Agents; D009287:Naphthyridines; D010726:Phosphodiesterase Inhibitors; D016210:Methacholine Chloride; D013395:Sucrose; C044843:AH 21-132