| pubmed-article:2666986 | pubmed:otherAbstract | PIP: A review of the agents tested in animals and men and shown to have a direct nonhormonal contraceptive effect is subdivided into those affecting spermatogenesis in the testis, sperm maturation in the epididymis, transport in the vas deferens and sperm functional activity via the accessory glands. Chemicals acting in the testis, sperm functional activity via the accessory glands. Chemicals acting in the testis, and tested in men, are bis(dichloracetyl)diamines, later found to have disulfuram-like effects, and nitrofurans, which had several systemic adverse effects. Gossypol acts at this levels, probably by affecting sperm mitochondria. It requires prolonged administration by oral route, and causes hypokalemia. Lonidamine, an indazole-carboxylic acid, was tested in men without reported side effects. Other agents tested in animals are thiophenes, dinitropyrroles, nitroimidazoles, organosiloxanes, indenopyridines, 5-thio-D-glucose, glycerol, ethionine and heavy metals, such as cadmium. Compounds active in the epididymis include sulfasalazine the prostaglandin synthesis inhibitor used for inflammatory bowel disease, as well as alpha-chlorohydrin, and several 6- cholor-deoxy-sugars which have been tried in animals only. Sulfasalazine cause s reversible sperm impairment, primarily enlarged sperm heads. The antifungal agent ketoconazole, a substituted imidazole acts at the level of the accessory glands, immobilizing sperm, but it also has several toxic effects if used on a long-term basis, notably central nervous system, liver and adrenal gland damage. Analogs of ketoconazole with greater antifertility effect and lesser toxicity are being sought. The approach of searching for drugs that act on the male reproductive tract directly without affecting hormonal regulation has not produced any candidates without systemic side effects, but it is hoped that it will provide agents with reversible metabolic effects peculiar to these target tissues. | lld:pubmed |
