The contraceptive effects of etoprine on male mice and rats.
We had previously found that 2,4-diaminopyrimidines affected spermatogenesis, possibly through the inhibition of testicular dihydrofolate reductase (DHFR). The current study examined the effects of etoprine, a highly lipophilic 2,4-diaminopyrimidine that is also a potent DHFR inhibitor, on the fertility of male mice at various dosages (0.1-50 mg/kg/day) for 55 days and male rats at 5 mg/kg/day for 65 days. Two other substituted diaminopyrimidines were tested at dosages of 50 mg/kg/day for 55 days. Results of breeding trials along with assessment of various parameters indicative of male fertility were noted. We found that of the compounds tested, etoprine is a potent antifertility agent that causes complete infertility at doses of > or = 5 mg/kg/day in mice with a threshold of effectiveness occurring between 1 and 5 mg/kg/day. The antifertility action of etoprine may be related to its capacity to inhibit testicular DHFR and its high degree of lipophilicity.
Malik
N S
NS
Department of Biology, Millersville University, Pennsylvania 17551, USA.
Matlin
S A
SA
Fried
J
J
Pakyz
R E
RE
Consentino
M J
MJ
D000818:Animals; D001835:Body Weight; D003272:Contraceptive Agents, Male / Q000494:pharmacology*; D004822:Epididymis / Q000166:cytology / Q000201:enzymology; D005298:Fertility / Q000187:drug effects; D005493:Folic Acid Antagonists / Q000494:pharmacology; D008297:Male; D051379:Mice; D009929:Organ Size; D011739:Pyrimethamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D013081:Sperm Motility / Q000187:drug effects; D013091:Spermatogenesis / Q000187:drug effects; D013094:Spermatozoa / Q000166:cytology / Q000187:drug effects
D003272:Contraceptive Agents, Male; D005493:Folic Acid Antagonists; C013909:etoprine; D011739:Pyrimethamine