Acetazolamide teratogenesis in Wistar rats: potentiation and antagonism by adrenergic agents.
Acetazolamide, a carbonic anhydrase inhibitor, induced right forelimb ectrodactyly in rat fetuses when the mothers were treated on late day 10 and early day 11 of gestation. Coadministration of the selective alpha-1-adrenergic agonist phenylephrine significantly increased the incidence of acetazolamide-induced right forelimb ectrodactyly while failing to induce the lesion when administered alone. Pretreatment with the alpha-adrenergic antagonists phenoxybenzamine and prazosin prevented the phenylephrine-induced increase in right forelimb ectrodactyly. In addition, treatment with either phenoxybenzamine or prazosin in the absence of stimulation with phenylephrine significantly decreased the incidence of acetazolamide-induced ectrodactyly. The results suggest an adrenergic component in acetazolamide teratogenesis. Alterations in uterine blood flow are discussed as a plausible mechanism for the modification of the incidence of ectrodactyly by these adrenergic agents.
D000014:Abnormalities, Drug-Induced / Q000209:etiology* / Q000517:prevention & control; D000086:Acetazolamide / Q000633:toxicity*; D000818:Animals; D005260:Female; D017880:Limb Deformities, Congenital; D010643:Phenoxybenzamine / Q000494:pharmacology; D010656:Phenylephrine / Q000633:toxicity; D011224:Prazosin / Q000494:pharmacology; D011247:Pregnancy; D051381:Rats; D011919:Rats, Inbred Strains; D012039:Regional Blood Flow / Q000187:drug effects; D013566:Sympathomimetics / Q000494:pharmacology / Q000633:toxicity*; D014599:Uterus / Q000098:blood supply
D013566:Sympathomimetics; D010643:Phenoxybenzamine; D010656:Phenylephrine; D000086:Acetazolamide; D011224:Prazosin