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Steric aspects of formoterol and terbutaline: Is there an adverse effect of the distomer on airway smooth muscle function?
Author(s) -
Källström BrittLouise,
Sjöberg Jacob,
Waldeck Bertil
Publication year - 1996
Publication title -
chirality
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.43
H-Index - 77
eISSN - 1520-636X
pISSN - 0899-0042
DOI - 10.1002/(sici)1520-636x(1996)8:8<567::aid-chir5>3.0.co;2-6
Subject(s) - chemistry , steric effects , terbutaline , formoterol , airway , adverse effect , function (biology) , pharmacology , medicine , asthma , stereochemistry , anesthesia , microbiology and biotechnology , biology , budesonide
Experiments were made on isolated tissues from guinea‐pig to test the hypothesis that the distomers of rac ‐β 2 ‐adrenoceptor agonists induce airway hyperreactivity. Tracheal strip preparations were contracted with carbachol. Both rac ‐ and (R;R)‐formoterol (2 and 1 μmol/1, respectively) produced an immediate relaxation, followed by a slow recovery of tone. (S;S)‐Formoterol (2 μmol/1) had no effect on smooth muscle tone. Similar results were obtained with the enantiomers of terbutaline. In other strip preparations of the trachea or the main bronchi, cholinergic or nonadrenergic/noncholinergic (NANC) excitatory responses were evoked by electrical field‐stimulation. The eutomers, (R;R)‐formoterol and (R)‐terbutaline, inhibited concentration‐dependently both cholinergic and NANC‐induced contractions. The distomers, (S;S)‐formoterol and (S)‐terbutaline, showed qualitatively the same effects but were about 1,000 times less potent than the corresponding eutomer. In a third series of experiments, either enantiomer of formoterol was administered to an electrically stimulated vagus nerve‐trachea tube preparation. The nerve‐induced contractions were inhibited by both enantiomers, but (S;S)‐formoterol was about 1,000 times less potent than (R;R)‐formoterol. For both enantiomers of formoterol, about tenfold higher concentration was required to obtain the same degree of inhibition when given intratracheally as compared with administration in the external medium. There was no indication in any of the experimental approaches that (S;S)‐formoterol or (S)‐terbutaline might enhance the response to cholinergic or NANC‐related stimuli. Chirality 8:567–573, 1996. © 1997 Wiley‐Liss, Inc.