Author:
MALIK NASIR S.,MATLIN STEPHEN A.,FRIED JOSEF,PAKYZ RUTH E.,CONSENTINO M. JAMES
Abstract
ABSTRACT: 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 ≥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.
Subject
Urology,Endocrinology,Reproductive Medicine,Endocrinology, Diabetes and Metabolism
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