Single-dose administration of the gonadotropin-releasing hormone antagonist, Nal-Lys (antide) to healthy men

To evaluate the ability the Nal-Lys GnRH antagonist ([N-Ac-Nal (2)1, 4ClDPhe2, D3Pal3, Lys (Nic)5, D-Lys(Nic)6, Lys (iPr)8, D-Ala10] to suppress gonadotropins and T in humans and to assess its duration of action and its local effects.Placebo-controlled clinical study.A university community.Seven normal male volunteers.We administered single injections of Nal-Lys (0, 10, 25, and 50 micrograms/kg body weight). Blood samples were collected before and at frequent time intervals after injection.Nal-Lys caused only minor local effects. At the higher doses (25 and 50 micrograms/kg), serum LH and T levels were suppressed to 50% to 70% of baseline; serum FSH levels were suppressed to 70% to 80% of baseline, and levels of all three hormones returned to basal values within 24 hours after injection.In humans, Nal-Lys has similar potency and duration of action to other antagonists and produces fewer local side effects. However, the utility of Nal-Lys is limited by formulation difficulties; current efforts are directed at improving the formulation in order to explore the potential clinical uses of this peptide.Gonadotropin-releasing hormone (GnRH) antagonists are synthetic analogues of GnRH which compete with endogenous GnRH for pituitary binding sites and cause immediate suppression of gonadotropin secretion and, secondarily, of gonadal steroid secretion in animals and men. They are potentially useful in a variety of clinical situations, including the induction of ovulation, prostate disease, and contraceptive development. The authors have shown that when these compounds are given to men on a daily basis, the suppression of hormone levels is maintained throughout the treatment period. The characteristics of long duration of action plus low histamine-releasing effects have made Nal-Lys a potentially attractive GnRH antagonist, but no data have been available on the use of the antagonist in humans. The authors therefore evaluated the ability of single doses of Nal-Lys to suppress gonadotropins and T in healthy young men, to assess its duration of action, and assess its local effects at the site of injection. Seven men aged 21-36 years received single injections of 0, 10, 25, and 50 mcg/kg body weight of Nal-Lys. Blood samples were collected before and at frequent time intervals after injection. Nal-Lys in this study was found to have potency and duration of action similar to other antagonists, while producing only minor local side effects. At 25 and 50 mcg/kg body weight, serum LH and T levels were suppressed to 50-70% of baseline; serum FSH levels were suppressed to 70-80% of baseline, and levels of all three hormones returned to basal values within 24 hours after injection. The utility of Nal-Lys, however, is limited by formulation difficulties. Current efforts are directed at improving the formulation in order to explore the potential clinical uses of the peptide.