Further Studies on the Antitesticular Activity of a Pipecolinomethylhydroxyindane

Abstract

Summary. Treatment with dl-6-(N-\g=a\-pipecolinomethyl)-5-hydroxyindane maleate (PMHI) depressed testis weights in immature rats, mice, hamsters and guinea-pigs. Similar effects on testicular weight were observed in adult rabbits, dogs and two species of monkey. Concurrent administration of testosterone, gonadotrophins, dl-tocopherol acetate, and methionine did not prevent the testicular weight reduction induced with PMHI in the immature rat. In hypophysectomized rats, the administration of PMHI caused further significant reduction in testicular weights. These data indicate that the activity of PMHI is directly on the testis and is not mediated by way of the hypothalamus\p=m-\pituitary\p=m-\ gonadal axis.

Permanent Sterility in the Male Rat After a Single Oral Dose of a Pipecolinomethylhydroxyindane

“…Sterility ensued from the 5th week and persisted to the termination of the experiment 20 weeks after dosing. The antitesticular activity of DL-6-(N-a-pipecolinomethyl)-5-hydroxyindane maléate (PMHI) in the rat and other species has been described (Boris, Ng & Hurley, 1974;Boris, DeMartino & Cox, 1974). These studies also indicated that treatment with PMHI for 21 days caused sterility in male rats, and that the reversibility of the antifertility effect depended on the dose which had been given.…”

Development of male‐fertility‐regulating agents

“…[91][92][93] It is active in rats by oral route. Dose for dose, it causes greater reduction in testicular weight than WIN 18446, nitrofurazone, methallibure, and diethylstilbestrol (DES), but less reduction in seminal vesicle and ventral prostate weight as produced by antigonadotrophic agents methallibure and DES.…”

“…In the in vitro cytocidal assay, where gossypol and apogossypol were found to be most active with half maximal inhibitory concentrations (IDw) of 6 pM and 3 pM, respectively, some other simpler compounds [SK 31517 (92), SK 31518 (93), SK 31520 (94), and SK 31588 (95)] were also significantly active with IDw of 13, 47, 13, and 18 pM, respectively.…”