The effect of the enantiomers of formoterol on inherent and induced tone in guinea-pig trachea and human bronchus

The long-acting beta(2)-adrenoceptor agonist formoterol is, like all other members of this class of drugs, used as a racemate in the clinic. While the effects of the individual enantiomers have been studied on airway smooth m uscle from guinea pig, comparable data on human bronchial smooth muscle are scanty or absent. Therefore, we compared the effects of the enantiomers of formoterol on inherent and induced tone in isolated human bronchi with tha t on guinea-pig trachea in vitro. The human bronchi either were studied und er resting tension conditions or were precontracted with 10 mu M carbachol or 0.1 mM histamine. The guinea-pig trachea was precontracted with 0.01, 0. 1 or 1 mu M carbachol. The racemate and (R,R)-formoterol caused a concentra rion-dependent relaxation of all preparations with an EC50 of about 1 nM. I n the guinea-pig trachea, the concentration-effect curve for formoterol was moved to the right in response to an increased concentration of carbachol. In both human bronchus and guinea-pig trachea, (S,S)-formoterol was more t han 1,000 times less potent than (R,R)-formoterol. Thus the relaxing effect of formoterol in human airways as well as in guinea-pig trachea was shown to lie with the (R,R)-enantiomer. Notably, (S,S)-formoterol did not exert a ny contractile effects within the tested concentration range in either airw ay preparation. Therefore, we conclude that with regard to relaxant effects the pure (R,R)-enantiomer of formoterol does not offer a benefit over the racemate.