INHIBITION OF ANTI-IGE INDUCED SKIN-RESPONSE IN NORMALS BY FORMOTEROL, A NEW BETA-2-ADRENOCEPTOR AGONIST, AND TERBUTALINE .2. EFFECT ON THE LATE PHASE REACTION

Formoterol, a new β2 selective long‐acting bronchodilator, was compared with terbutaline in terms of ability to inhibit dual phase skin reactions to anti‐human IgE in volunteers. Anti‐IgE induced an early wheal and flare reaction (WFR) followed by a progressively increasing induration, the late phase reaction (LCR), lasting 24 h. Intradermal injection of formoterol 20 ng or terbutaline 500 ng 5 min before challenge gave equal inhibition of the WFR. The subsequent LCR was suppressed by formoterol (30 %) for the whole 24 h period, while terbutaline only attenuated the first 4 h period. Increasing the dose range of both drugs 25‐fold, caused a further analogous reduction of the WFR to anti‐IgE. In this higher dose range formoterol (0.5 ng) antagonized the following 1–24 h LCR by 50 %, while terbutaline (25 μg) only attenuated the LCR by an average of 20 %, with higher effect in the first 6 h period. The anti‐LCR capacity of formoterol was highly superior to that of terbutaline (P < 0.001). The histamine‐elicited wheal response was attenuated by both drugs, but they had no effect on the flare response, favouring an anti‐permeability action of both compounds. The data support the concept that terbutaline, given locally in a single dose shortly before challenge, inhibits the mast cell mediator release reaction with limited consequences for the following LCR. In contrast to terbutaline, formoterol exerted a substantial anti‐LCR action, probably by interfering with inflammatory mechanisms after the initial mast cell mediator release. Copyright © 1990, Wiley Blackwell. All rights reserved