Tocolytic effects of a long-acting beta2-adrenoceptor agonist, formoterol, in rats.

We have assessed the tocolytic activity of formoterol, a novel long-acting and potent beta2-adrenoceptor agonist, through its production of cyclic adenosine monophosphate, in comparison with ritodrine, a beta2-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 x 10(-10) and 4.7 x 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 beta-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.