Reproductive/endocrine and anaphylactoid properties of an LHRH-antagonist, ORF 18260 [Ac-DNAL1(2), 4FDPhe2,D-Trp3,D-Arg6]-GnRH.

It has been demonstrated in a variety of experiments that ORF 18260 inhibits (ED100) spontaneous and LHRH-induced ovulation in rats (10 micrograms/kg s.c.; 10 mg/kg i.g.) and hamsters (100 micrograms/kg s.c. and 100 mg/kg i.g.). Inhibition of LHRH induced ovulation appears to be competitive in nature. In normally cycling animals, efficacy varies with time of administration. In the spontaneously ovulating rat, the most effective time is 15.00 hr of proestrus; in the hamster it is 10.00 hr. Continuous administration inhibits ovulation in rats, and ORF 18260 has contragestational activity in rats and hamsters but not in guinea pigs and mice. Prostate growth in rats is inhibited at a dose of 100 micrograms/kg (s.c.). Our studies also suggest that ORF 18260 can also induce cutaneous anaphylactoid-like reactions in rats. When compound is administered intradermally in rats, ORF 18260 causes a dose-related whealing response, noticeable from the 0.01 micrograms/rat dose level.