Brammer Matthew K, Gilmore Deborah L, Matsumoto Rae R
Department of Pharmaceutical Sciences, College of Pharmacy, University of Oklahoma Health Sciences Center, Oklahoma City, OK, 73190 USA.
Eur J Pharmacol. 2006 Dec 28;553(1-3):141-5. doi: 10.1016/j.ejphar.2006.09.038. Epub 2006 Sep 28.
Methamphetamine and 3,4-methylenedioxymethamphetamine (MDMA) are structurally similar and represent a serious and growing health threat. Earlier studies in our laboratory have shown that methamphetamine interacts with sigma receptors and that antagonism of these receptors can attenuate methamphetamine-induced locomotor stimulation and neurotoxicity. However, no research exists which characterizes the interaction between sigma receptors and MDMA. Therefore, the goal of the present study was to determine whether sigma receptors are involved in the actions of MDMA. In the first part of the study, competition and saturation binding assays were performed to measure the interaction of MDMA with sigma receptors. The receptor binding assays revealed that MDMA interacts preferentially with the sigma(1) subtype, as compared to the sigma(2) subtype, and that this interaction occurs in a competitive manner. The second part of the study focused on behavioral measurements in male, Swiss Webster mice to determine whether a selective sigma(1) receptor antagonist, BD1063 (1-[2-(3,4-dichlorophenyl)ethyl]-4-methylpiperazine, 0-30 mg/kg, i.p.) could attenuate the locomotor stimulant actions of MDMA (0-50 mg/kg, i.p.). BD1063 alone had no effect on locomotor activity, but dose-dependently attenuated the locomotor stimulant effects of MDMA and produced a significant shift to the right in the MDMA dose response curve. Together, the data support the functional relevance of the interaction of MDMA with sigma(1) receptors, and suggest that these receptors are involved in the stimulant actions of MDMA.
甲基苯丙胺和3,4-亚甲基二氧甲基苯丙胺（摇头丸）结构相似，对健康构成的威胁日益严重。我们实验室早期的研究表明，甲基苯丙胺与σ受体相互作用，拮抗这些受体会减弱甲基苯丙胺引起的运动兴奋和神经毒性。然而，目前尚无研究描述σ受体与摇头丸之间的相互作用。因此，本研究的目的是确定σ受体是否参与摇头丸的作用。在研究的第一部分，进行了竞争和饱和结合试验，以测量摇头丸与σ受体的相互作用。受体结合试验表明，与σ₂亚型相比，摇头丸优先与σ₁亚型相互作用，且这种相互作用以竞争方式发生。研究的第二部分集中于对雄性瑞士韦伯斯特小鼠的行为测量，以确定选择性σ₁受体拮抗剂BD1063（1-[2-(3,4-二氯苯基)乙基]-4-甲基哌嗪，0-30 mg/kg，腹腔注射）是否能减弱摇头丸（0-50 mg/kg，腹腔注射）的运动兴奋作用。单独使用BD1063对运动活性没有影响，但能剂量依赖性地减弱摇头丸的运动兴奋作用，并使摇头丸剂量反应曲线显著右移。总之，这些数据支持了摇头丸与σ₁受体相互作用的功能相关性，并表明这些受体参与了摇头丸的兴奋作用。
