Problems of acetazolamide and N‐ethylnicotinamide as teratogens

Abstract

Abstract Experiments with acetazolamide and N‐ethylnicotinamide were made by injection into the yolk sac of chicken eggs after 24 and 96 hours of incubation. Acetazolamide produced in both stages abnormalities of the upper beak, the dosage‐effect response following a linear course. Effects minor in incidence were rumplessness at 24 hours, bending of tibiotarsus shaft in both stages and muscular hypoplasia after 96 hours. N‐ethylnicotinamide led to abnormalities of the upper beak in both stages. to malformations of tibiotarsus and fibula at 96 hours. With increasing dosages the results of N‐ethylnicotinamide rose by threshold effects. In a particular strain of White Leghorn fowl embryos gave little or no response to acetazolamide; N‐ethylnicotinamide produced the usual incidence of long bone defects, but few beak abnormalities. Acetazolamide acted as protective supplement when added to treatment with sulfanilamide; it prevented all abnormalities (micromelia) of long bones; it reduced incidence of defects of upper and lower beak after treatment at 24 hours, but not those of upper beak after 96 hours. N‐ethylnicotinamide also gave complete protection against sulfanilamide‐induced abnormality of lower beak and long bones, but an increased incidence of shortened upper beak. Acetazolamide and N‐ethylnicotinamide injected together at 96 hours led to exaggeration in incidence and change in expressivity of defects of the upper beak and a drastic lowering in frequency of tibiotarsus‐fibula malformations. Supplements of ADP reduced toxicity of acetazolamide and incidence of defects of the upper beak produced by it. Interference with NAD functions and oxidative phosphorylation is likely to be the cause of the teratogenic effects of acetazolamide as well as N‐ethylnicotinamide.