title: Inhibition of anti-IgE induced skin response in normals by formoterol, a new beta 2-adrenoceptor agonist, and terbutaline. 1. Dose response relation and duration of effect on the early wheal and flare response.
abstract: The intention of the present study was to compare formoterol and terbutaline regarding ability to inhibit immediate wheal and flare responses (WFR) to anti-human IgE with focus on the duration of anti-WFR action. Formoterol is a novel beta 2-adrenergic agonist with a prolonged duration of bronchodilation capacity after inhalation. The drugs injected intradermally 2 min prior to challenge with anti-IgE in volunteers produced a dose-dependent inhibition of the WFR in the range 1pg-100ng (formoterol) and 1ng-1 microgram (terbutaline). Formoterol was 70 times (flare) and 25 times (wheal) more potent (ID40) than terbutaline on a weight basis. The duration of the anti-WFR action for formoterol, injected in a 25 times lower dose than terbutaline, was significantly longer, namely greater than 24 h versus 8 h for terbutaline. The histamine-induced wheal reaction was attenuated by 15% and 25% by terbutaline and formoterol, respectively. The results indicate a higher beta 2-receptor activity for formoterol with respect to inhibition of IgE-dependent mast cell mediator release in addition to an anti-leak effect exerted by both drugs. The prolonged duration of antagonistic effect by formoterol on the WFR to anti-IgE might be due to the lipophilic property of the drug, with an expected higher retention of formoterol at the target tissue compared with the more hydrophilic compound terbutaline.
authors.affiliation: Department of Lung Medicine, Huddinge University Hospital, Sweden.
authors.forename: R
authors.initials: R
authors.lastname: Grönneberg
authors.forename: O
authors.initials: O
authors.lastname: Zetterström
mesh_terms: D000318:Adrenergic beta-Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D000328:Adult; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology*; D004305:Dose-Response Relationship, Drug; D004983:Ethanolamines / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D000068759:Formoterol Fumarate; D006801:Humans; D007073:Immunoglobulin E / Q000276:immunology*; D007271:Injections, Intradermal; D008407:Mast Cells; D008875:Middle Aged; D012867:Skin / Q000187:drug effects / Q000276:immunology*; D013726:Terbutaline / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D000318:Adrenergic beta-Agonists; D000888:Antibodies, Anti-Idiotypic; D004983:Ethanolamines; D007073:Immunoglobulin E; D013726:Terbutaline; D000068759:Formoterol Fumarate