Delineation of mu-antagonist, partial kappa agonist and non-opioid agonist activity of cyclazocine using urinary output of rats.

The effects of cyclazocine (SC) were studied under a variety of test conditions to determine its various activities on urinary output. Cyclazocine antagonized the morphine-induced (20 mg/kg) antidiuretic effect in water-loaded (3 ml/100 g b.wt.) rats at low doses (0.08, 0.16 and 0.32 mg/kg). At higher doses (1.25, 5 and 20 mg/kg), cyclazocine caused diuresis in normally hydrated rats. The diuresis produced by 1.25 and 5, but not 20 mg/kg, was antagonized by naloxone (10 mg/kg). In water-deprived rats and in normally hydrated rats, cyclazocine, in a dose-related fashion, antagonized the diuretic effects of 0.08 mg/kg of bremazocine. These results are compatible with the interpretation that cyclazocine has mu-antagonist activity at low doses, then partial kappa-agonist activity at intermediate doses, followed by non-opioid agonist activities at the higher doses.