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.
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.
Grönneberg
R
R
Department of Lung Medicine, Huddinge University Hospital, Sweden.
Zetterström
O
O
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*
D000318:Adrenergic beta-Agonists; D000888:Antibodies, Anti-Idiotypic; D004983:Ethanolamines; D007073:Immunoglobulin E; D013726:Terbutaline; D000068759:Formoterol Fumarate