ANTIFERTILITY POTENTIAL OF ORNIDAZOLE ANALOGS IN RATS

In order to determine which part of the ornidazole molecule chloro-2-h ydroxy)propyl-2-methyl-5-nitroimidazole] is responsible for its antife rtility action, structural analogues were fed to male rats of proven f ertility at doses equivalent to the antifertility dose of ornidazole ( 1.82 mmol/kg/day). The fertility of the males was tested, before oral gavage (control mating) and after 10 and 14 days of feeding, by counti ng the number of fetuses and corpora lutea present in females 12 days after mating. The day after the last mating, the kinematic parameters of sperm from the cauda epididymidis were assessed objectively with a Hamilton-Thorne motility analyzer. Analogues bearing the 2-nitro and 5 -methyl groups on the imidazole ring were inactive if the (chlorohydro xy)propyl group were substituted by proton or methyl, hydroxyethyl, ch loroethyl, or (sulfonylethyl)ethyl groups, indicating that the three-c arbon side chain of ornidazole was necessary for the antifertility act ion. Only ornidazole and its acetate were effective antifertility agen ts, but a compound bearing the (chlorohydroxy)propyl side chain attach ed to a nitrogen atom of a heterocyclic phthalimide produced a partial but temporary reduction in fertility. Similarities of the action of o midazole with the male antifertility agent, alpha-chlorohydrin [3-chlo ro-1,2-propanediol], are discussed.