CM156, a high affinity sigma ligand, attenuates the stimulant and neurotoxic effects of methamphetamine in mice.
CM156, a high affinity sigma ligand, attenuates the stimulant and neurotoxic effects of methamphetamine in mice.
复制标题
DOI：
10.1016/j.neuropharm.2011.06.028
复制
发表时间：
2011-10
影响因子：
4.7
通讯作者：
Matsumoto, Rae R.
中科院分区：
文献类型：
--
作者：
Kaushal, Nidhi;Seminerio, Michael J.;Shaikh, Jamaluddin;Medina, Mark A.;Mesangeau, Christophe;Wilson, Lisa L.;McCurdy, Christopher R.;Matsumoto, Rae R.
甲基苯丙胺（METH）是一种高度成瘾的精神兴奋剂药物。低剂量和高剂量给予METH分别导致运动刺激和多巴胺能和多巴胺能神经毒性。METH的行为刺激和神经毒性作用可导致成瘾和其他神经精神障碍，因此需要确定针对METH产生的这些作用的潜在药物治疗剂。METH在生理相关浓度下与σ受体结合。此外，σ受体存在于多巴胺能神经元和多巴胺能神经元上并且可以调节多巴胺能神经元和多巴胺能神经元。因此，σ受体为开发针对METH的不良作用的药物治疗剂提供了可行的靶标。在本研究中，CM 156是一种对σ受体具有高亲和力和选择性的σ受体配体，超过了80个其他非σ结合位点，对MET诱导的刺激，过热和神经毒性作用进行了评价。用CM 156对雄性瑞士韦伯斯特小鼠进行预处理，剂量依赖性地减弱了METH产生的运动刺激、体温过高、纹状体多巴胺和5-羟色胺耗竭以及纹状体多巴胺和5-羟色胺转运体减少，而CM 156本身没有显著影响。这些结果证明了高选择性σ配体减轻METH影响的能力。
Methamphetamine (METH) is a highly addictive psychostimulant drug of abuse. Low and high dose administration of METH leads to locomotor stimulation, and dopaminergic and serotonergic neurotoxicity, respectively. The behavioral stimulant and neurotoxic effects of METH can contribute to addiction and other neuropsychiatric disorders, thus necessitating the identification of potential pharmacotherapeutics against these effects produced by METH. METH binds to σ receptors at physiologically relevant concentrations. Also, σ receptors are present on and can modulate dopaminergic and serotonergic neurons. Therefore, σ receptors provide a viable target for the development of pharmacotherapeutics against the adverse effects of METH. In the present study, CM156, a σ receptor ligand with high affinity and selectivity for σ receptors over 80 other non-σ binding sites, was evaluated against METH-induced stimulant, hyperthermic, and neurotoxic effects. Pretreatment of male, Swiss Webster mice with CM156 dose dependently attenuated the locomotor stimulation, hyperthermia, striatal dopamine and serotonin depletions, and striatal dopamine and serotonin transporter reductions produced by METH, without significant effects of CM156 on its own. These results demonstrate the ability of a highly selective σ ligand to mitigate the effects of METH.
登录
查看更多内容
DOI：
10.1186/1471-2210-6-6
发表时间：
2006-03-03
期刊：
BMC pharmacology
影响因子：
--
作者：
Han DD;Gu HH
通讯作者：
Gu HH
影响因子：
5.3
作者：
Kaushal N;Matsumoto RR
通讯作者：
Matsumoto RR
DOI：
10.1124/jpet.106.101527
发表时间：
2006-06-01
影响因子：
3.5
作者：
Meunier, Johann;Ieni, John;Maurice, Tangui
通讯作者：
Maurice, Tangui
影响因子：
5.6
作者：
Matsumoto, Rae R.;Shaikh, Jamaluddin;Coop, Andrew
通讯作者：
Coop, Andrew
影响因子：
2.9
作者：
Imam, SZ;Crow, JP;Ali, SF
通讯作者：
Ali, SF