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Modification by betamethasone of the effects of bronchodilator drugs on cholinergic bronchoconstriction in rats
Author(s) -
Mattila M.J.,
Salonen R.O.
Publication year - 1984
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.1476-5381.1984.tb16214.x
Subject(s) - bronchoconstriction , bronchodilator , ipratropium bromide , methacholine , betamethasone , bradycardia , agonist , pharmacology , bronchodilator agents , medicine , terbutaline , anesthesia , chemistry , asthma , heart rate , lung , receptor , respiratory disease , blood pressure
1 Effects of betamethasone (BM), a long‐acting glucocorticoid, given alone and in combination with bronchodilator drugs, terbutaline (Ter), theophylline (Theo), or ipratropium bromide (Ipra), were studied on dose‐related methacholine (MeCh 2, 3, and 4.5 μg i.v.)‐induced bronchoconstriction in anaesthetized rats. BM (0.4 or 2 mg kg −1 ) was given intraperitoneally 24 h before the experiment followed by a similar dose intravenously, 12 min before MeCh challenge. The bronchodilator drugs were given i.v. as acute single doses. 2 BM 0.4 mg kg −1 counteracted significantly MeCh‐induced bronchoconstriction without modifying MeCh‐induced transient bradycardia and hypotension. BM 2 mg kg −1 failed to improve that response. A time interval of 24 h after pre treatment proved mandatory to produce these effects. 3 Combined treatment with BM 0.4 mg kg −1 + Ter 20 μg kg −1 antagonized the MeCh‐induced bronchoconstriction in an additive manner at 2 and 3 μg of MeCh, but a synergistic interaction was found at the largest MeCh dose. The effects of the other combinations (BM 0.4 mg kg −1 + Theo 20 mg kg −1 and BM 0.4 mg kg −1 + Ipra 0.5 μg kg −1 ) on airways failed to exceed the expected sum of the individual drugs. 4 The combination of BM + Ter was selective to the airways only, whereas BM + Theo also counteracted MeCh‐induced bradycardia and BM + Ipra counteracted both hypotension and bradycardia. 5 It is concluded that combined treatment with glucocorticoid and β 2 ‐adrenoceptor agonist may result in a synergistic interaction on severe airway obstruction without significant influence on cardiovascular system.