Tocolytic Effects of a Long-acting β2-Adrenoceptor Agonist, Formoterol, in Rats

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Abstract
We have assessed the tocolytic activity of formoterol, a novel long-acting and potent β2-adrenoceptor agonist, through its production of cyclic adenosine monophosphate, in comparison with ritodrine, a β2-adrenoceptor agonist used clinically to counter premature delivery. Formoterol and ritodrine inhibited the amplitude and frequency of rat uterine contraction, with IC50 values of 3.8 times 10−10 and 4.7 times 10−7 M, respectively. Intravenous administration of formoterol or ritodrine caused inhibition of uterine motility and increased heart rate in a dose-dependent manner. Inhibition of uterine motility by oral administration of formoterol (0.3 and 1 mg kg−1) continued for at least 60 min, whereas that with ritodrine (100 mg kg−1) persisted for 15 min with rapid recovery thereafter in pregnant rats. The β-adrenoceptor binding of [125I]iodopindolol to the myometrium of pregnant rats was competitive with formoterol and ritodrine, with Ki values of 0.04 and 6.10 nM, respectively. Formoterol (10−6 — 10−4 M) and ritodrine (10−6 — 10−4 M) increased the level of cyclic adenosine monophosphate in lymphocytes in a dose-dependent manner. The results suggested that formoterol caused relaxation of uterine motility through production of cyclic adenosine monophosphate. Thus, formoterol may be useful as a treatment to counter premature delivery.