Picenadol, a mixed opioid agonist/antagonist without κ opioid agonist activity in the rat urination test

Picenadol and its (+) and (−) isomers were compared to butorphanol and nalbuphine for their effects on urinary output in the normally hydrated rat. Butorphanol, a partial K agonist, increased urinary output markedly at all doses (0.32–20 mg/kg, s.c.). Nalbuphine (0.32–20 mg/kg, s.c.), picenadol (1.25–40 mg/kg, s.c.) and the two isomers (0.32–20 mg/kg, s.c.) had no tendency to increase urinary output within the 5‐hr test period. Nalbuphine did not affect bremazocine‐induced diuresis, whereas the (−) isomer of picenadol decreased bremazocine‐induced diuresis through a κ‐antagonist action and the (+) isomer of picenadol decreased the bremazocine‐induced diuresis through a μ‐opioid‐like agonist action. These results were interpreted to mean that nalbuphine is a mixed agonist/antagonist without activity at κ receptors. Picenadol is a mixed agonist/antagonist with potent μ‐opioid action in the (+) isomer and weak μ‐and κ‐antagonist action in the (−) isomer.