Targeting sigma receptors: novel medication development for drug abuse and addiction.
Targeting sigma receptors: novel medication development for drug abuse and addiction.
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DOI：
10.1586/ecp.09.18
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发表时间：
2009-07
影响因子：
4.4
通讯作者：
Matsumoto RR
中科院分区：
文献类型：
--
作者：
Matsumoto RR
精神兴奋剂滥用在工业化国家和发展中国家是一个严重的健康和社会问题。然而，确定一种有效的药物疗法来治疗它仍然难以捉摸。人们早就知道，许多精神兴奋剂药物，包括可卡因和甲基苯丙胺，与大脑和心脏中的sigma受体相互作用，为药物开发工作提供了一个合乎逻辑的目标。然而，选择性药理学试剂和分子生物学工具最近才成为可用于严格评估这些受体作为可行的药物开发目标。目前的审查将总结挑衅性的临床前数据，证明西格玛受体拮抗剂和反义寡核苷酸的能力，以改善可卡因诱导的惊厥，致死率，自发活动和致敏，和条件性位置偏好的啮齿动物。最近的研究表明，σ受体拮抗剂的保护作用也延伸到甲基苯丙胺、3，4-亚甲二氧基甲基苯丙胺、乙醇和其他滥用物质产生的作用。总之，这些数据表明，靶向σ受体，特别是σ1亚型，可能为对抗可卡因以及其他滥用物质的影响提供了一种创新方法。
Psychostimulant abuse is a serious health and societal problem in industrialized and developing countries. However, the identification of an effective pharmacotherapy to treat it has remained elusive. It has long been known that many psychostimulant drugs, including cocaine and methamphetamine, interact with sigma receptors in the brain and heart, offering a logical target for medication development efforts. However, selective pharmacological agents and molecular biological tools have only recently become available to rigorously evaluate these receptors as viable medication development targets. The current review will summarize provocative preclinical data, demonstrating the ability of sigma receptor antagonists and antisense oligonucleotides to ameliorate cocaine-induced convulsions, lethality, locomotor activity and sensitization, and conditioned place-preference in rodents. Recent studies suggest that the protective effects of sigma receptor antagonists also extend to actions produced by methamphetamine, 3,4-methylenedioxymethamphetamine, ethanol and other abused substances. Together, the data indicate that targeting sigma receptors, particularly the σ1-subtype, may offer an innovative approach for combating the effects of cocaine, and perhaps other abused substances.