Effects of the novel opiate antagonist, SDZ 210-096, on luteinizing hormone secretion in the rat
Siegel, R.A.; Révész, L.
Journal of Pharmacology and Experimental Therapeutics 249(1): 264-270
1989
ISSN/ISBN: 0022-3565 PMID: 2540315 Document Number: 328257
SDZ 210-096 is a novel 14 beta-benzyl morphinan derivative with antagonistic actions at mu and kappa opiate receptors. In the present experiments this compound has been characterized for luteinizing hormone (LH) secretion-stimulating effects in a variety of experimental paradigms in the rat. In juvenile female rats, serum LH levels were elevated markedly after s.c. or p.o. administration of SDZ 210-096; ED50 was less than 1 mg/kg p.o. at 60 min. Similar effects were seen in the male rat, with p.o. ED50 values of 1.5 and 2.8 mg/kg at 60 and 120 min, respectively. Serum LH levels were likewise elevated by this compound in adult female rats (both proestrous and diestrous). SDZ 210-096 maintained its LH secretion-stimulating capability in both male and female rats after up to 10 days of administration. Its effects were inhibited in a competitive manner by a mu (SDZ 202-250) and a kappa (bremazocine) opiate agonist. Moderate effects on prolactin and adrenocorticotropic hormone secretion (inhibition and stimulation, respectively) were observed. SDZ 210-096 exhibited specific high affinity binding to brain opiate binding sites. These results demonstrate that in the rat SDZ 210-096 is a potent, p.o.-active LH secretion stimulator, effective after repeated as well as acute application.