The embryotoxicity of a new class of antispermatogenic agents: the 3-indazole-carboxylic acids.
The effects of two antispermatogenic 3-indazole-carboxylic acids on pregnancy in the rat have been studied. AF 1312/TS (1-(4-chlorobenzyl)-1H-indazole-3-carboxylic acid) when administered from day 6 to day 15 of pregnancy produced embryolethality with an LD50 of 145 mg/kg. The more potent antispermatogenic lonidamine was 7.25 times more effective, with an LD50 of 20 mg/kg. No significant teratogenicity was exerted by AF 1312/TS, whilst lonidamine was slightly effective only at embryolethal doses. The latter was also effective after a single administration on day 9, with an embryonal LD50 of 25 mg/kg, whereas the teratogenic effect was greatest on day 10. The similarity of the embryonal LD50 after single or repeated administrations suggests an interference with a specific epigenetic crisis.
D000818:Animals; D000988:Antispermatogenic Agents / Q000633:toxicity*; D001522:Behavior, Animal / Q000187:drug effects; D004622:Embryo, Mammalian / Q000187:drug effects*; D005260:Female; D005313:Fetal Death / Q000139:chemically induced; D005333:Fetus / Q000187:drug effects*; D005865:Gestational Age; D007191:Indazoles / Q000633:toxicity*; D007928:Lethal Dose 50; D011247:Pregnancy; D011720:Pyrazoles / Q000633:toxicity*; D051381:Rats
D000988:Antispermatogenic Agents; D007191:Indazoles; D011720:Pyrazoles; C007762:1-p-chlorobenzyl-1H-indazole-3-carboxylic acid; C016371:lonidamine