Habenicht U F, Schneider M R, el Etreby M F
Research Laboratories of Schering AG, Berlin, F.R.G.
J Steroid Biochem Mol Biol. 1990 Dec 20;37(6):937-42. doi: 10.1016/0960-0760(90)90447-s.
The ability of the new LHRH antagonist antide to induce a long-term chemical castration in adult male rats and cynomolgus monkeys was investigated. The animals were treated subcutaneously with different doses either once or on 5 consecutive days. The effects on serum concentration of LH (only rat) and testosterone and on the weights of the testes, prostates and seminal vesicles were investigated after different periods of time. Histological evaluation of testes, pituitary and hypothalamus was also performed. In the rat a clear dose-dependent inhibitory effect on the above mentioned parameters was observed whereby long-lasting castration-like effects were achieved at concentrations between 6 (less than or equal to 8 weeks) and 15 mg/kg (greater than 8 weeks). In the cynomolgus monkey a prolonged inhibitory effect was induced only at 15 mg/kg and the duration was only 2-3 weeks. Histologically, no signs indicative of irreversible effects were observed in either species.
although species differences became evident in terms of the duration of a long-lasting inhibitory effect on the male reproductive system, antide exhibited such an effect in the rat and the monkey and was able to induce a chemical castration in both species. In addition, using the rat Dunning R 3327 prostatic carcinoma model, 10 mg/kg antide given subcutaneously every 6 weeks for a total period of 26 weeks, had an inhibitory effect on tumor growth identical to that of castration emphasizing the suitability of this compound for treatment of prostatic cancer.
研究了新型促黄体激素释放激素（LHRH）拮抗剂antide在成年雄性大鼠和食蟹猴中诱导长期化学去势的能力。动物分别单次或连续5天皮下注射不同剂量的药物。在不同时间段后，研究了对血清促黄体生成素（LH，仅在大鼠中检测）和睾酮浓度以及对睾丸、前列腺和精囊重量的影响。还对睾丸、垂体和下丘脑进行了组织学评估。在大鼠中，观察到对上述参数有明显的剂量依赖性抑制作用，在6mg/kg（小于或等于8周）至15mg/kg（大于8周）的浓度下可实现持久的去势样效果。在食蟹猴中，仅在15mg/kg时诱导出延长的抑制作用，且持续时间仅为2 - 3周。组织学上，在两个物种中均未观察到不可逆效应的迹象。
尽管在对雄性生殖系统的长期抑制作用持续时间方面物种差异明显，但antide在大鼠和猴子中均表现出这种作用，并且能够在两个物种中诱导化学去势。此外，使用大鼠Dunning R 3327前列腺癌模型，每6周皮下注射10mg/kg的antide，共26周，对肿瘤生长的抑制作用与去势相同，强调了该化合物对前列腺癌治疗的适用性。
