EFFECT OF THE NEW POTENT LHRH ANTAGONIST ANTIDE

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 (> 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. In conclusion: 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, 10mg/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.