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.
D000818:Animals; D002746:Chlorpromazine / Q000633:toxicity; D002972:Cleft Palate / Q000139:chemically induced; D005260:Female; D005333:Fetus / Q000187:drug effects*; D006220:Haloperidol / Q000633:toxicity; D010546:Perphenazine / Q000633:toxicity; D010879:Piperazines / Q000633:toxicity*; D051381:Rats; D013329:Structure-Activity Relationship; D013723:Teratogens / Q000633:toxicity*
D010879:Piperazines; D013723:Teratogens; D010546:Perphenazine; D006220:Haloperidol; D002746:Chlorpromazine