CARDIOVASCULAR TERATOGENICITY OF TERBUTALINE AND RITODRINE IN THE CHICK-EMBRYO

OBJECTIVE: We determined the teratogenic effects of terbutaline and ri todrine, both beta(2)-sympathomimetic agonists, on the stage 24 (4-day ) chick embryo. STUDY DESIGN: We used a topical method of application of terbutaline or ritodrine to the stage 24 chick embryo in ovo. Doses of terbutaline ranged from 5.5 x 10(-10) to 6.5 x 10(-9) mol per embr yo, and ritodrine doses ranged from 4.6 x 10(-11) to 4.6 x 10(-8) mol per embryo. To further determine the pharmacologic nature of the terat ogenic potential of terbutaline or ritodrine, the experiments were rep eated after pretreatment with butoxamine hydrochloride, a preferential beta(2)-antagonist, or metoprolol tartrate, a preferential beta(1)-an tagonist, 4 hours before application of terbutaline or ritodrine. RESU LTS: Terbutaline treatment was associated with significantly higher ra tes of anomalies than in controls at all dosages used, whereas ritodri ne induced significantly more anomalies at or above doses of 4.6 x 10( -9) mol per embryo. At an equimolar dose pretreatment with butoxamine hydrochloride significantly reduced the cardiovascular teratogenic eff ects of terbutaline and ritodrine. Pretreatment with metoprolol tartra te at any dose did not significantly reduce terbutaline's potential. M etoprolol, at doses tenfold or 100-fold higher than ritodrine, was abl e to significantly reduce the teratogenic effects of ritodrine. CONCLU SIONS: Our data suggest that terbutaline and ritodrine are teratogenic in the chick and that these agents exert their teratogenic effects pr imarily through stimulation of the beta 2-adrenergic receptor.