Seppälä T, Idänpään-Heikkilä J J, Strömberg C, Mattila M J
Laboratory of Pharmacology and Toxicology, National Public Health Institute, Helsinki, Finland.
Life Sci. 1994;55(3):245-51. doi: 10.1016/0024-3205(94)00886-8.
The interactions of an alpha 2-adrenoceptor antagonist, atipamezole, and an alpha 2-adrenoceptor agonist, dexmedetomidine, with ethanol were studied in male NIH Swiss mice. The mice were given (i.p.) atipamezole 0.1, 0.3, 1, 3 and 10 mg/kg and dexmedetomidine 0.01, 0.03, 0.1, 0.3, 1, 3 and 10 mg/kg; the ethanol doses were 1, 2 or 3 g/kg. Motor performance was measured by spontaneous locomotor activity and rotarod test. Dexmedetomidine impaired performance in both tests. The effect of dexmedetomidine peaked at the dose of 1 mg/kg. Three mg/kg of atipamezole abolished totally the effects of 0.3 mg/kg of dexmedetomidine and partially those of 1 mg/kg of dexmedetomidine. Atipamezole counteracted and dexmedetomidine enchanced ethanol effects in both tests. The interactions were not of pharmacokinetic origin since blood and brain ethanol and dexmedetomidine levels were unaltered at the time of testing. The results suggest that ethanol effects on motor performance in mice are mediated in part via central noradrenergic mechanisms, and blockade of alpha 2-adrenoceptors by atipamezole leads to considerable antagonism of these ethanol effects.
在雄性NIH瑞士小鼠中研究了α2 -肾上腺素能受体拮抗剂阿替美唑和α2 -肾上腺素能受体激动剂右美托咪定与乙醇的相互作用。给小鼠腹腔注射0.1、0.3、1、3和10mg/kg的阿替美唑以及0.01、0.03、0.1、0.3、1、3和10mg/kg的右美托咪定；乙醇剂量为1、2或3g/kg。通过自发运动活动和转棒试验测量运动性能。右美托咪定在两项试验中均损害了性能。右美托咪定的作用在1mg/kg剂量时达到峰值。3mg/kg的阿替美唑完全消除了0.3mg/kg右美托咪定的作用，并部分消除了1mg/kg右美托咪定的作用。在两项试验中，阿替美唑抵消了乙醇的作用，而右美托咪定增强了乙醇的作用。这些相互作用并非源于药代动力学，因为在测试时血液和大脑中的乙醇及右美托咪定水平未发生改变。结果表明，乙醇对小鼠运动性能的影响部分是通过中枢去甲肾上腺素能机制介导的，阿替美唑对α2 -肾上腺素能受体的阻断导致这些乙醇作用产生显著拮抗。
