Prolonged anti-luteinizing hormone/follicle-stimulating hormone-releasing activities of some synthetic antagonists of luteinizing hormone-releasing hormone.

A number of synthetic analogs of luteinizing hormone-releasing hormone (LH-RH) were screened for their in vivo antigonadotropin-releasing activities using a four-point bioassay test in immature male rats. Of the peptides tested, the most effective were those containing D-phenylalanine in position 2 of the decapeptide chain in conjunction with D-leucine or, preferably, D-phenylalanine in position 6. Several inhibitory peptides that were found to be very potent were reassayed and compared for duration of inhibition in immature male rats, whereupon the D-Phe2 analogs were found to be particularly long-acting. The most active and persistent peptide of the series, [D-Phe2, D-Phe6]-LH-RH, was able to inhibit the response to exogenous LH-RH for up to 6 hours after its injection.