title: Cardiovascular teratogenicity of terbutaline and ritodrine in the chick embryo.
abstract: OBJECTIVE
  We determined the teratogenic effects of terbutaline and ritodrine, both beta 2-sympathomimetic agonists, on the stage 24 (4-day) chick embryo.
  
  
  METHODS
  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 embryo, 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 teratogenic potential of terbutaline or ritodrine, the experiments were repeated after pretreatment with butoxamine hydrochloride, a preferential beta 2-antagonist, or metoprolol tartrate, a preferential beta 1-antagonist, 4 hours before application of terbutaline or ritodrine.
  
  
  RESULTS
  Terbutaline treatment was associated with significantly higher rates of anomalies than in controls at all dosages used, whereas ritodrine 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 effects of terbutaline and ritodrine. Pretreatment with metoprolol tartrate at any dose did not significantly reduce terbutaline's potential. Metoprolol, at doses tenfold or 100-fold higher than ritodrine, was able to significantly reduce the teratogenic effects of ritodrine.
  
  
  CONCLUSIONS
  Our data suggest that terbutaline and ritodrine are teratogenic in the chick and that these agents exert their teratogenic effects primarily through stimulation of the beta 2-adrenergic receptor.
authors.affiliation: Department of Cellular Biology and Anatomy, Medical College of Wisconsin, Milwaukee.
authors.forename: D R
authors.initials: DR
authors.lastname: Lenselink
authors.forename: R S
authors.initials: RS
authors.lastname: Kuhlmann
authors.forename: J M
authors.initials: JM
authors.lastname: Lawrence
authors.forename: G L
authors.initials: GL
authors.lastname: Kolesari
mesh_terms: D000818:Animals; D002078:Butoxamine / Q000494:pharmacology; D002642:Chick Embryo; D004305:Dose-Response Relationship, Drug; D006330:Heart Defects, Congenital / Q000139:chemically induced*; D008790:Metoprolol / Q000494:pharmacology; D011943:Receptors, Adrenergic, beta / Q000187:drug effects; D012312:Ritodrine / Q000633:toxicity*; D013726:Terbutaline / Q000633:toxicity*
chemical_list: D011943:Receptors, Adrenergic, beta; D002078:Butoxamine; D008790:Metoprolol; D012312:Ritodrine; D013726:Terbutaline