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.