Effects of the novel opiate antagonist, SDZ 210-096, on luteinizing hormone secretion in the rat.
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.
Siegel
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RA
Preclinical Research, Pharma Division, Sandoz AG, Basle, Switzerland.
Révész
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D000324:Adrenocorticotropic Hormone / Q000378:metabolism; D000818:Animals; D004305:Dose-Response Relationship, Drug; D005260:Female; D007986:Luteinizing Hormone / Q000378:metabolism*; D008297:Male; D009019:Morphinans / Q000494:pharmacology*; D009292:Narcotic Antagonists / Q000494:pharmacology*; D011388:Prolactin / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011957:Receptors, Opioid / Q000187:drug effects; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu
D009019:Morphinans; D009292:Narcotic Antagonists; D011957:Receptors, Opioid; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; C059335:SDZ 210-096; D000324:Adrenocorticotropic Hormone; D011388:Prolactin; D007986:Luteinizing Hormone