Experimental teratogenicity of structurally similar compounds with or without piperazine-ring: a preliminary report.

For studying if piperazine-ring plays a role in teratogenicity pairs of compounds of similar structure and action (perphenazine-chloropromazine, chlorcyclizine--thenalidine, haloanisone--haloperiodol) had been selected, where only one of them contained piperazine-ring. The applied single doses were 3.7 X 10(-4) M/kg. Experiments were carried out on Wistar/H-Riop pregnant rats; equimolar doses of three drug-pairs were given orally on the 13th, 14th, or 15th gestational days, respectively. Perphenazine and chlorcyclizine, as alkyl-piperazine derivatives induced cleft palate and micromelia, while chlorpromazine and thenalidine did not. After the methoxyphenyl-piperazine containing substance--haloanisone--micromelia was higher as compared to that containing no piperazine moiety (haloperidol). These results indicate that the piperazine-ring may play an important role in the teratogenicity of drugs in rats.

The fetal alcohol syndrome: symptoms and pathogenesis.

The symptoms of the fetal alcohol syndrome and their frequency of appearance are described based on 41 reports in the literature and on own observations. Experimental evidence is presented proving the lack of cytotoxicity, mutagenicity and teratogenicity of alcohol itself and the intensive cytotoxicity, mutagenicity and teratogenicity of acetaldehyde. Responsibility for the fetal alcohol syndrome is ascribed to acetaldehyde at maternal blood concentrations surpassing 35 micrometer and it is suggested that the raised acetaldehyde level is due to an inherited or acquired defect of mitochondrial aldehyde dehydrogenase. Prospective mothers displaying acetaldehyde levels exceeding 30 micrometer after a drink should be advised against bearing a child.