Spermicidal effect of antagonists of platelet-activating factor

A variety of antagonists of platelet-activating factor (PAF) have been examined for their ability to prevent pregnancy, by admixture with spermatozoa in vitro followed by insemination, or in vivo by administration to female rabbits. When the antagonists were added to the ejaculate at a concentration of 10(-4) M 30 minutes before insemination of the females, a significant failure of fertilization was seen only with CV-3988, U66985, and SRI 63-441--all structural analogs of PAF. Antagonists that were not structural analogs were not effective. All compounds to a lesser or greater extent caused some qualitative agglutination and loss of sperm motility, but these effects were not correlated with inhibition of fertilization. SRI 63-441 was the most effective compound and was subjected to further study. When given intravenously prior to ovulation (5 mg/kg at 1, 5, and 9 hours after the ovulating injection), no effect on fertilization was seen. If SRI 63-441 (40 mg in 0.5 ml aqueous solution) was instilled into the vagina 2 minutes before insemination, a highly significant reduction in the fertilization rate was achieved. It is concluded that these compounds act by an action on the sperm membrane rather than by direct PAF antagonism on spermatozoa.