Inhibitory effect of a new opioid agonist on reproductive endocrine activity in rats of both sexes.

Morphine and other opioid compounds such as the new benzomorphan derivative, bremazocine, inhibit the secretion of luteinizing hormone in rats of both sexes (1, 2, 3, 4). The aim of our work was to compare in rats the LH-secretion inhibiting properties of bremazocine, a putative opiate kappa agonist (5), with those of the mu agonist morphine. Acute administration of bremazocine (0.005 - 1 mg/kg s.c.) or of morphine (10 - 20 mg/kg s.c.) diminished serum LH levels and spontaneous ovulation in female rats in a dose-dependent manner. Chronic treatment with bremazocine significantly diminished LH and testosterone secretions in male rats which in turn led to a fall in weight of the prostate gland; prolactin and FSH secretions were not influenced significantly. The mu-antagonist naloxone, which increases LH release in rats, in acute experiments significantly antagonized the inhibiting effect of morphine, but not that of bremazocine on LH secretion. Neither the basal nor the LHRH-stimulated secretion of LH in pituitary cell cultures were changed by bremazocine (10(-11) to 10(-5) M), however the release of LHRH-like activity from hypothalamic fragments was significantly impaired by 10(-7) M bremazocine. In conclusion, the data presented here show that bremazocine is a new non-morphine-like opioid agonist which selectively inhibits LH release in rats.