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l-1, 4-Dimethyl-10-hydroxy-2, 3, 4, 5, 6, 7-hexahydro-1, 6-methano-1H-4-benzazonine hydrobomide (l-ST-2121) is a new narcotic-antagonist analgesic possessing remarkable analgesic activity, and this activity is equal to or more potent than that of pentazocine. A single administration of l-ST-2121 produced a moderate CNS depression in rats, such as sedation, systemic muscle relaxation and decrease in motor activity. Rats were intermittently mediated for 1 to 6 days at one hour intervals through an implanted intravenous cannula. In a physical dependence producing test, physical dependence on morphine was developed rapidly in the rats maintained with as low as 9.6 mg/kg/day. Physical dependence on pentazocine and l-ST-2121 was also developed with the maintenance dose of 96 mg/kg/day, but not with 9.6 mg/kg/day. However, physical dependence on pentazocine was developed with the maintenance dose of 19.2 mg/kg/day, but l-ST-2121 was not. In a naloxone-precipitated withdrawal test, rats treated with l-ST-2121 (24 mg/kg/day, 48 mg/kg/day and 96 mg/kg/day) showed withdrawal signs when they were given naloxone. Rats treated with morphine or pentazocine also showed withdrawal signs after naloxone challenge. In a substitution test, l-ST-2121 suppressed the withdrawal signs of morphine- and pentazocine-dependent rats, and pentazocine suppressed those of morphine-dependent rats. l-ST-2121 has physical dependence liability of morphine type. The results show that all three drugs induce physical dependence in the order of severity of morphine greater than pentazocine greater than or equal to l-ST-2121.

journal of toxicological sciences

PHYSICAL DEPENDENCE LIABILITY TEST OF l-1, 4-DIMETHYL-10-HYDROXY-2, 3, 4, 5, 6, 7-HEXAHYDRO-1, 6-METHANO-1H-4-BENZAZONINE HYDROBROMIDE (l-ST-2121) IN RATS