The effect of the enantiomers of formoterol on inherent and induced tone in guinea-pig trachea and human bronchus.
The long-acting beta2-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 muscle 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 that on guinea-pig trachea in vitro. The human bronchi either were studied under resting tension conditions or were precontracted with 10 microM carbachol or 0.1 mM histamine. The guinea-pig trachea was precontracted with 0.01, 0.1 or 1 microM carbachol. The racemate and (R,R)-formoterol caused a concentration-dependent relaxation of all preparations with an EC50 of about 1 nM. In 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 than 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 any contractile effects within the tested concentration range in either airway 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.
Schmidt
D
D
Leiden University Medical Center, Department of Pulmonology, The Netherlands.
Källström
B L
BL
Waldeck
B
B
Branscheid
D
D
Magnussen
H
H
Rabe
K F
KF
D000318:Adrenergic beta-Agonists / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D001980:Bronchi / Q000187:drug effects* / Q000502:physiology; D001993:Bronchodilator Agents / Q000737:chemistry / Q000494:pharmacology*; D002217:Carbachol / Q000494:pharmacology; D004983:Ethanolamines / Q000737:chemistry / Q000494:pharmacology*; D000068759:Formoterol Fumarate; D006168:Guinea Pigs; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D009126:Muscle Relaxation; D009129:Muscle Tonus / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D018343:Receptors, Adrenergic, beta-2 / Q000187:drug effects; D013237:Stereoisomerism; D014132:Trachea / Q000187:drug effects* / Q000502:physiology
D000318:Adrenergic beta-Agonists; D001993:Bronchodilator Agents; D004983:Ethanolamines; D018343:Receptors, Adrenergic, beta-2; D002217:Carbachol; D000068759:Formoterol Fumarate