Teratogenic action of acetazolamide in golden hamsters

The carbonic‐anhydrase inhibitor acetazolamide was teratogenic for golden hamsters when given in single intraperitoneal doses of from 300‐1200 mg/kg on the 9th day of pregnancy. Most deformities were of the postaxial part of the forelimb. There was a well‐defined dose‐response relation with an ED50 of 695 mg/kg. A sensitive period was demonstrated from 192–210 hours after mating with a peak at 204 hours. The production of this deformity was not associated with a significant embryonic mortality. Acetazolamide is quite specific in that in addition to hand deformities only a few foot deformities and rare cases of exencephaly were produced. In contrast to rats, where acetazolamide‐induced deformities are almost exclusively of the postaxial portion of the right forelimb, the deformity in hamsters occurred in either forelimb, although when a single hindfoot was malformed it was always the left one. The demonstrated sensitive period is during the time of limbbud formation, and the first external signs of deformity were seen as a flattening of the postaxial margins of the limb bud 24 hours after drug administration. The mechanism of action of acetazolamide is not clear since the teratogenic dose probably exceeds the amount needed for complete inhibition of carbonic‐anhydrase activity. The dose needed is also much greater than that used for human therapy, so it does not appear that this drug is a teratogenic hazard for human beings.