Comparison of the antigonadotropic activity of three GnRH antagonists (Nal-Glu, Antide and Cetrorelix) in a non-human primate model (Macaca fascicularis).
We compared the antigonadotropic activity of the GnRH antagonists Nal-Glu, Antide and Cetrorelix in a non-human primate model (Macaca fascicularis). Orchidectomized animals received a single subcutaneous injection at doses of 250 micrograms kg-1 (n = 4), 625 micrograms kg-1 (n = 4) and 1250 micrograms kg-1 (n = 3) of the compounds Nal-Glu ([Ac-D-Nal(2)1, D-4-Cl-Phe2, D-Pal3, Arg5, D-Glu(AA)6, D-Ala10]-GnRH), Antide (Nal-Lys, [Ac-D-Nal1, D-4-Cl-Phe2, D-Pal3, Nic-Lys5, D-Nic-Lys6, Ip-Lys8, D-Ala10]-GnRH) or Cetrorelix ([Ac-D-Nal1, D-4-Cl-Phe2, D-Pal3, D-Cit6, D-Ala10]-GnRH). Blood samples were collected before and 3, 6, 12, 24, 48, 72, and 96 h after GnRH antagonist administration. Serum was analysed for concentrations of bioactive LH and immunoactive LH and FSH. All three compounds decreased LH secretion within 3-12 h (P < 0.05) and FSH secretion within 12-48 h (P < 0.05) after injection. Major differences between the GnRH antagonists were observed with regard to the effective dose and duration of action. At a dose of 250 micrograms kg-1 Nal-Glu and Antide only transiently suppressed LH and FSH release, whereas Cetrorelix induced complete inhibition (P < 0.05) which lasted for the entire observation period. At a dose of 625 micrograms kg-1 Cetrorelix exhibited the longest duration of action and Nal-Glu the shortest. At the highest dose of 1250 micrograms kg-1 Nal-Glu, Antide and Cetrorelix markedly inhibited LH and FSH secretion throughout the entire study period.(ABSTRACT TRUNCATED AT 250 WORDS)
Weinbauer
G F
GF
Institute of Reproductive Medicine of the University, Münster, Germany.
Nieschlag
E
E
D000818:Animals; D005640:Follicle Stimulating Hormone / Q000097:blood / Q000378:metabolism*; D007987:Gonadotropin-Releasing Hormone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D007700:Kinetics; D007986:Luteinizing Hormone / Q000097:blood / Q000378:metabolism*; D008252:Macaca fascicularis; D008297:Male; D009842:Oligopeptides / Q000008:administration & dosage / Q000494:pharmacology*; D009919:Orchiectomy
C057805:LHRH, N-Ac-2-Nal(1)-4-Cl-Phe(2)-3-Pal(3)-Arg(5)-Glu(6)-AlaNH2(10)-; D009842:Oligopeptides; D007987:Gonadotropin-Releasing Hormone; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; C057022:iturelix; C062876:cetrorelix