Beyler S A, Zaneveld L J
Contraception. 1982 Aug;26(2):137-46. doi: 10.1016/0010-7824(82)90082-8.
Low molecular weight, synthetic proteinase inhibitors that inhibit sperm-associated acrosin, were released systemically in female mice at a constant rate from minipumps. The release was timed so that, after mating, the minipumps were depleted of inhibitor before blastocyst implantation took place. Three of the inhibitors: 4-aminobenzamidine (ABD), 4-nitrophenyl-4-guanidino-benzoate (NPGB) and 4-methylumbelliferone-4-guanidinobenzoate (MUGB) caused a 50% decrease in fertility, the last two at very low concentrations. The fourth inhibitor, benzamidine (BD), which is also the weakest inhibitor of mouse acrosin and in vitro fertilization, had no effect. These results show that at least one of the processes leading to fertilization or early blastogenesis, is dependent on proteolytic activity and that the systemic application of proteinase inhibitors inhibits conception. MUGB possessed low toxicity and a high margin of safety, encouraging the development of phenol derivatives of guanidinobenzoic acid as contraceptive agents.
低分子量的合成蛋白酶抑制剂可抑制与精子相关的顶体蛋白酶，通过微型泵以恒定速率在雌性小鼠体内全身释放。释放时间经过设定，以便在交配后，微型泵中的抑制剂在胚泡着床前耗尽。其中三种抑制剂：4-氨基苯甲脒（ABD）、4-硝基苯基-4-胍基苯甲酸酯（NPGB）和4-甲基伞形酮-4-胍基苯甲酸酯（MUGB）使生育力降低了50%，后两种在非常低的浓度下即可起效。第四种抑制剂苯甲脒（BD），它也是小鼠顶体蛋白酶和体外受精的最弱抑制剂，没有效果。这些结果表明，导致受精或早期胚泡形成的过程中至少有一个依赖于蛋白水解活性，并且蛋白酶抑制剂的全身应用会抑制受孕。MUGB具有低毒性和高安全系数，这促使胍基苯甲酸的酚类衍生物作为避孕剂得到开发。
