Pharmacological mechanisms of naltrexone and acamprosate in the prevention of relapse in alcohol dependence
Pharmacological mechanisms of naltrexone and acamprosate in the prevention of relapse in alcohol dependence
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DOI：
10.1111/j.1521-0391.2003.tb00492.x
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发表时间：
2003-01-01
影响因子：
3.7
通讯作者：
Zieglgänsberger, W
中科院分区：
文献类型：
--
作者：
Littleton, J;Zieglgänsberger, W
纳洛酮和阿坎酸可能最终被证明是有用的补充药物治疗酒精中毒，减少复发。纳洛酮是μ-阿片受体的相对选择性竞争性拮抗剂，这种活性可以解释其抗复发作用，因为内源性阿片类物质参与酒精的正强化作用和/或因为这些相同的递质参与这些作用的条件性预期。相比之下，阿坎酸的药理学仍然知之甚少。这并不奇怪，因为它是一种小的灵活分子，与几种神经活性氨基酸相似，并且以高剂量使用。所有这些因素都表明，它可能具有多种作用。目前，对阿坎酸作用的最佳解释似乎是，它抑制了参与酒精的负强化作用和条件性“假戒断”的多巴胺能递质系统，这在线索诱导的复发中可能是重要的。
Naltrexone and acamprosate may ultimately prove to be useful additions to pharmacotherapy for alcoholism by reducing relapse. Naltrexone is a relatively selective competitive antagonist at mu-opioid receptors, and this activity may explain its anti-relapse action either because endogenous opioids are involved in the positively reinforcing effects of alcohol and/or because these same transmitters are involved in the conditioned anticipation of these effects. In contrast, the pharmacology of acamprosate is still poorly understood. This is not surprising because it is a small flexible molecule with similarities to several neuro-active amino acids and is used in high doses. All these factors suggest that it may have multiple actions. Currently, the best explanation for the effects of acamprosate seems to be that it inhibits the glutamatergic transmitter system involved in both the negative reinforcing effects of alcohol and the conditioned "pseudo-withdrawal" that may be important in cue-induced relapse.