Pharmacological studies with cetrorelix (SB-75), a potent antagonist of luteinising hormone-releasing hormone.
The antitumour and hormone-suppressive effects of the luteinising hormone-releasing hormone LH-RH antagonist Cetrorelix (D-20761) and its pamoate salt (D-20762) were investigated in the model of the DMBA-induced mammary carcinoma of female rats and by testosterone determinations in normal male rats. Treatment with single high doses of D-20761 induced a rapid decrease of tumour weights with a dose-dependent duration of action. Strong antitumour effects were also observed by applying different multiple dose schedules, including a initial high dose (3.16 mg/kg, s.c.) followed by a low maintenance dose (31.6 micrograms/kg, s.c.). The stability of the molecule against degrading enzymes led to the idea of using the poorly soluble pamoate salt for facilitating a sustained release of active compound. This salt indeed induced a prolonged suppression of tumour growth and of testosterone levels. In conclusion, we found that Cetrorelix is a highly effective LH-RH antagonist which should be further developed for the treatment of hormone-dependent diseases.
Reissmann
T
T
Central Research & Development ASTA Medica AG, Dresden, Germany.
Klenner
T
T
Deger
W
W
Hilgard
P
P
McGregor
G P
GP
Voigt
K
K
Engel
J
J
D000818:Animals; D004305:Dose-Response Relationship, Drug; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors* / Q000097:blood / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy*; D010447:Peptide Hydrolases / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013739:Testosterone / Q000032:analysis
D007987:Gonadotropin-Releasing Hormone; D013739:Testosterone; D010447:Peptide Hydrolases; C062876:cetrorelix