Hoffer A P, Agarwal A, Meltzer P, Naqvi R, Matlin S A
Harvard Program in Urology (Brigham and Women's Hospital), Boston, MA.
Contraception. 1988 Mar;37(3):301-31. doi: 10.1016/0010-7824(88)90032-7.
Because there are problems, in men, associated with the use of gossypol related to reversibility and, infrequently, hypokalemia, several laboratories around the world have resorted to the synthesis and evaluation of experimental analogs and optical isomers of gossypol in an attempt to find a compound which retains its pharmacologically desirable antifertility effects while eliminating its suboptimal ones. The present study documents: (a) the effects of fourteen new, orally-administered synthetic analogs of gossypol on testicular ultrastructure and fertility in hamsters, (b) the in vitro effects of these compounds as well as of the optical isomers of gossypol against hamster and human sperm, and (c) the morphological and antifertility effects of intratesticular injections of gossypol-PVP and its optimal isomers in the rat. The results of the study demonstrate that these new analogs are not effective as male antifertility agents and that their in vitro activity is unrelated to their in vivo contraceptive potential. In addition, this report establishes the validity of the intratesticular injection model for the analysis of the mechanism of action of gossypol and its analogs by making these compounds directly available at the testicular site. The significance of these findings is discussed.
由于棉酚在男性使用方面存在与可逆性相关的问题，且偶尔会出现低钾血症，世界各地的几个实验室已着手合成和评估棉酚的实验类似物及旋光异构体，试图找到一种既能保留其药理学上理想的抗生育作用，又能消除其不理想作用的化合物。本研究记录了：(a) 十四种新的口服合成棉酚类似物对仓鼠睾丸超微结构和生育力的影响，(b) 这些化合物以及棉酚旋光异构体对仓鼠和人类精子的体外作用，以及 (c) 棉酚 - 聚乙烯吡咯烷酮及其最佳异构体在大鼠睾丸内注射的形态学和抗生育作用。研究结果表明，这些新类似物作为男性抗生育剂无效，且它们的体外活性与其体内避孕潜力无关。此外，本报告通过使这些化合物直接作用于睾丸部位，确立了睾丸内注射模型用于分析棉酚及其类似物作用机制的有效性。讨论了这些发现的意义。
