Suppression of plasma gonadotropins by abarelix: A potent new LHRH antagonist

Abarelix (PPI-149) is the decapeptide N-Ac-D-Nal(2)-D-pCl-Phe-D-Pal(3)-Ser- NM-Tyr-Asn-Leu-ILys-Pro-Gly-NH2. This compound is a novel, potent competiti ve luteinizing hormone-releasing hormone (LHRH) antagonist with a high wate r solubility and low induction of histamine release, Abarelix administered via continuous infusion induces a rapid decrease in the plasma concentratio n of testosterone that is maintained throughout the course of administratio n of the antagonist. The drop in plasma testosterone is accompanied by a co rresponding decrease in the plasma levels of the gonadotropins luteinizing hormone (LH) and follicle-stimulating hormone (FSH), The LHRH agonists curr ently used in the treatment of prostate cancer induce a large increase in p lasma levels of gonadotropins and gonadal steroids prior to downregulating pituitary gonadotropin secretion. This study compares the initial stimulato ry effects of the LHRH agonist leuprolide in rats with the rapid suppressio n of plasma testosterone, LH, and FSH induced by abarelix.