Kalant H, Khanna J M, Llewellyn M, Rinkel G J, Woodworth I
Acta Psychiatr Scand Suppl. 1986;329:54-65. doi: 10.1111/j.1600-0447.1986.tb10536.x.
Tolerance to the effects of chlormethiazole on circular maze performance, and cross-tolerance to ethanol, were investigated in rats. Tolerance to chlormethiazole in the moving belt test was also measured in the same rats. Treatment with a total daily dose of subcutaneous chlormethiazole, 200 mg/kg, for 20 days produced clear tolerance to chlormethiazole and cross-tolerance to ethanol in the circular maze test. This treatment, however, failed to produce tolerance to chlormethiazole in the moving belt test. No evidence of physical dependence was found. In other studies, continuous intravenous infusion of chlormethiazole, 30-50 mg/kg/h for 9 days, resulted in clear functional tolerance to chlormethiazole and cross-tolerance to ethanol in the moving belt test. Similarly, chronic ethanol treatment, 4-6 g/kg daily for 3 weeks, resulted in functional tolerance to ethanol and cross-tolerance to chlormethiazole in the same test. These results indicate that the demonstration of functional tolerance to chlormethiazole and cross-tolerance to ethanol is dependent both on the sensitivity of the behavioural measurement tests employed, and on the degree of continuity of exposure of the central nervous system to the drug. It is concluded that, for doses that are equipotent in acute log-dose studies, chlormethiazole produces less tolerance and physical dependence than ethanol, perhaps because of a shorter half-life.
在大鼠中研究了对氯美噻唑对环形迷宫行为表现的耐受性以及对乙醇的交叉耐受性。同时也在这些大鼠中测量了在移动带试验中对氯美噻唑的耐受性。每日皮下注射氯美噻唑总剂量200mg/kg，持续20天的治疗在环形迷宫试验中产生了对氯美噻唑的明显耐受性以及对乙醇的交叉耐受性。然而，这种治疗在移动带试验中未能产生对氯美噻唑的耐受性。未发现身体依赖性的证据。在其他研究中，以30 - 50mg/kg/h的速度持续静脉输注氯美噻唑9天，在移动带试验中产生了对氯美噻唑的明显功能性耐受性以及对乙醇的交叉耐受性。同样，每日4 - 6g/kg的慢性乙醇治疗持续3周，在同一试验中产生了对乙醇的功能性耐受性以及对氯美噻唑的交叉耐受性。这些结果表明，对氯美噻唑的功能性耐受性和对乙醇的交叉耐受性的表现既取决于所采用的行为测量试验的敏感性，也取决于中枢神经系统对药物暴露的持续程度。得出的结论是，对于在急性对数剂量研究中效价相等的剂量，氯美噻唑产生的耐受性和身体依赖性比乙醇少，这可能是因为其半衰期较短。
