Activities of Antagonists of the Luteinizing Hormone Releasing Hormone with Emphasis on Positions 1, 5 and 6 and on Positions 1, 2 and 3

Folkers, Karl; Bowers, Cyril Y.; Xiao, Shaobo; Tang, Pui-Fun Louisa; Kubota, Minoru; Stępiński, Janusz; Kubiak, Teresa M.

doi:10.1515/znb-1987-0120

Cited by 5 publications

(1 citation statement)

References 12 publications

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“…The compound Nal-Glu (Rivier et al, 1986) was used in several clinical studies (reviewed by Nieschlag et al, 1992 and but caused local induration and erythema. The GnRH antagonists Antide (Folkers et al, 1987) and Cetrorelix (Bajusz et al, 1988a) were reported to induce a smaller histamin release than previous GnRH antagonists (Bajusz et al, 1988b;Philips et al, 1988). Non-human primate studies demonstrated that Antide is a potent inhibitor of pituitary and testicular function when administered chronically to male monkeys (Weinbauer et al, 1989).…”

Section: Introductionmentioning

confidence: 94%

Comparison of the antigonadotropic activity of three GnRH antagonists (Nal-Glu, Antide and Cetrorelix) in a non-human primate model (Macaca fascicularis)

Weinbauer¹,

Nieschlag²

2009

Andrologia

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We compared the antigonadotropic activity of the GnRH antagonists Nal-Glu, Antide and Cetrorelix in a non-human primate model (Macacafascicularis) . Orchidectomized animals received a single subcutaneous injection at doses of 250 pg kg-' (n = 4), 625 pg kg-' (n = 4) and 1250 pg kg-' (n = 3) of the compounds Nal-Glu ([Ac-D-Nal(2) ', D-Ala"] -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 (PC0.05) 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 pg kg-' 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 pg kg-' Cetrorelix exhibited the longest duration of action and Nal-Glu the shortest. At the highest dose of 1250 pg kg-' Nal-Glu, Antide and Cetrorelix markedly inhibited LH and FSH secretion throughout the entire study period. With Nal-Glu (625 and 1250 pg kg-') bioactive LH secretion appeared more reduced compared to immunoactive LH. In conclusion, Nal-Glu, Antide and Cetrorelix are potent inhibitors of LH and FSH secretion. In terms of the effective dose and duration of action Cetrorelix appeared most active, followed by Antide and Nal-Glu in this experimental model. Thus, Antide and Cetrorelix are highly interesting for clinical use.

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Section: Introductionmentioning

confidence: 94%