Abstract
l-1, 4-Dimethyl-10-hydroxy-2, 3, 4, 5, 6, 7-hexahydro-1, 6-methano-1H-4-benzazonine hydrobromide (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 inter-mittently medicated 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-2l2l was not. In a naloxone-precipitated withdrawal test, rats treated with l-ST-2121 (24mg/kg/day, 48mg/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-212l has physical dependence liability of morphine type. The results show that all three drugs induce physical dependence in the order of severity of morphine>pentazocine≥l-ST-2121.
