Teratological assessment of stobadine after single and repeated administration in mice.
Teratological studies were performed with stobadine, a compound with antiarrhythmic and antihypoxic activity. Single i.v. injections of stobadine in the form of dihydrochloride (DH 1011) to ICR mice on days 3, 6, 9 or 12 of gestation at doses of 1 and 3 mg kg-1 had no teratogenic effect. Slight fetal toxicity was manifested by decreased fetal weight after treatment on days 3 and 6, increased incidence of rudimentary ribs after treatment on days 9 and 12 of gestation and non-significantly increased postimplantation loss after injection on day 6 of gestation. The effect of repeated oral administration in the form of dipalmitate salt (DP 1031) was studied in doses of 12.2, 61.0 and 122.0 mg kg-1 on days 4-16 of gestation. Oral exposure to 61.0 mg kg-1 DP 1031 resulted in significant reduction of implantations, live fetuses and litter weight, and after 122.0 mg kg-1 DP 1031 the fetal weight was significantly decreased. External and skeletal examinations of the fetuses revealed no evidence of teratogenesis. The relevance of the two routes of stobadine administration for risk involvement is discussed.
Ujházy
E
E
Institute of Experimental Pharmacology, SAS, Bratislava, Slovak Republic.
Dubovický
M
M
Balonová
T
T
Jansák
J
J
Zeljenková
D
D
D000284:Administration, Oral; D000818:Animals; D001842:Bone and Bones / Q000002:abnormalities / Q000187:drug effects; D002243:Carbolines / Q000008:administration & dosage / Q000633:toxicity*; D005314:Embryonic and Fetal Development / Q000187:drug effects; D005260:Female; D007275:Injections, Intravenous; D008098:Litter Size / Q000187:drug effects; D008431:Maternal-Fetal Exchange / Q000502:physiology; D051379:Mice; D008813:Mice, Inbred ICR; D011247:Pregnancy; D013723:Teratogens / Q000633:toxicity*
D002243:Carbolines; D013723:Teratogens; C100106:dicarbine