Zornoza Teodoro, Cano María J, Polache Ana, Granero Luis
Department of Pharmaceutics, Faculty of Pharmacy, University of Valencia, Spain.
CNS Drug Rev. 2003 Winter;9(4):359-74. doi: 10.1111/j.1527-3458.2003.tb00260.x.
In the last years important advances have been made in the development of drugs for the treatment of alcohol addiction. Acamprosate (calcium bis-acetylhomotaurine) is one of the better established drugs in this field on the European market. This review focuses first on the pharmacokinetics of acamprosate. The published data and the recent advances in our knowledge on the mechanisms involved in the intestinal absorption and elimination of this drug are summarized. The importance of pharmacokinetics for the proper clinical use of acamprosate is highlighted. The anti-relapse as well as the well-known effects of acamprosate on ethanol intake are discussed. The recent experiments in animal models of conditioned withdrawal are reviewed. These experiments, explored for the first time the anticraving effect of the drug. Finally, the proposed hypotheses on the neuropharmacological mechanism of action of acamprosate are discussed. The discussion deals with the relative importance of various hypotheses as well as with the recent experiments that support them. It is pointed out that further research is necessary in order to clearly understand the mode of action of acamprosate as well as the neurobiological mechanisms involved in alcohol dependence.
近年来,在用于治疗酒精成瘾的药物研发方面取得了重要进展。阿坎酸(双乙酰高牛磺酸钙)是欧洲市场上这一领域中较成熟的药物之一。本综述首先聚焦于阿坎酸的药代动力学。总结了已发表的数据以及我们在该药物肠道吸收和消除所涉及机制方面知识的最新进展。强调了药代动力学对阿坎酸合理临床应用的重要性。讨论了阿坎酸的抗复发作用以及其对乙醇摄入的众所周知的影响。回顾了近期在条件性戒断动物模型中的实验。这些实验首次探究了该药物的抗渴望作用。最后,讨论了关于阿坎酸神经药理学作用机制的提出的假说。该讨论涉及各种假说的相对重要性以及支持它们的近期实验。指出有必要进行进一步研究,以便清楚地了解阿坎酸的作用方式以及酒精依赖所涉及的神经生物学机制。