Acetazolamide teratogenesis in Wistar rats: Potentiation and antagonism by adrenergic agents

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Abstract
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. Pretreatement 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.
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