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

Abstract

Objective: 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. Design: Placebo-controlled clinical study. Setting: A university community. Subjects: Seven normal male volunteers. Interventions: We administered single injections of Nal-Lys (0, 10, 25, and 50 μg/kg body weight). Blood samples were collected before and at frequent time intervals after injection. Results: Nal-Lys caused only minor local effects. At the higher doses (25 and 50 μg/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. Conclusions: 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.