The muscarinic receptor agonist xanomeline has an antipsychotic-like profile in the rat.
The muscarinic receptor agonist xanomeline has an antipsychotic-like profile in the rat.
复制标题
毒蕈碱受体激动剂 xanomeline 在大鼠中具有类似抗精神病药的作用。
DOI：
--
复制
发表时间：
2001
影响因子：
3.5
通讯作者：
A. Wyatt
中科院分区：
文献类型：
--
作者：
K. Stanhope;N. Mirza;M. Bickerdike;J. Bright;N. Harrington;M. Hesselink;G. Kennett;S. Lightowler;M. Sheardown;R. Syed;R. Upton;G. Wadsworth;S. Weiss;A. Wyatt
毒蕈碱受体激动剂xanomeline进行了检查，并与抗精神病药氯氮平和/或氟哌啶醇在以下体内大鼠模型：阿扑吗啡诱导的前脉冲抑制（PPI），安非他明诱导的hypermotortion，和条件性情绪反应（CER）测试中断。还在大鼠内侧前额叶皮质中离体评估了咕诺美林对多巴胺周转的影响。在不同剂量和前脉冲强度的条件下，与氟哌啶醇一样，xanomeline对PPI没有影响。与此相反，毒蕈碱受体拮抗剂东莨菪碱和毒蕈碱受体激动剂毛果芸香碱均诱导PPI显着的剂量依赖性赤字。氟哌啶醇和xanomeline，但不是毛果芸香碱，剂量依赖性逆转阿扑吗啡诱导的PPI中断。因此，咕诺美林在PPI中诱导了明确的抗精神病样作用，而毛果芸香碱似乎诱导了拟精神病样作用。在对自发活动无影响的剂量下，Xanomeline可减弱苯丙胺诱导的活动过度，这可能表明边缘系统多巴胺能功能亢进的减弱与运动不足的诱导之间存在差异。氟哌啶醇和氯氮平也能逆转安非他明诱导的过度运动，但剂量与减少自发运动的剂量相似。在CER试验中，氯氮平而非氟哌啶醇具有抗焦虑样作用。在CER试验中，克诺美林的作用与氯氮平相似，尽管在抗焦虑剂量下，它倾向于破坏杠杆按压的基线水平。最后，氟哌啶醇，氯氮平，毛果芸香碱，和xanomeline，都引起了内侧前额叶皮质多巴胺周转的增加。在这里使用的动物模型中，克诺美林的抗精神病样作用表明，它可能是一种有用的精神病治疗方法。
The muscarinic receptor agonist xanomeline was examined and compared with the antipsychotics clozapine and/or haloperidol in the following in vivo rat models: apomorphine-induced disruption of prepulse inhibition (PPI), amphetamine-induced hyperlocomotion, and the conditioned emotional response (CER) test. The effects of xanomeline were also assessed ex vivo on dopamine turnover in the rat medial prefrontal cortex. Under conditions of varying dose and prepulse intensity, xanomeline, like haloperidol, had no effect on PPI. In contrast, the muscarinic receptor antagonist scopolamine and the muscarinic receptor agonist pilocarpine both induced significant dose-dependent deficits in PPI. Haloperidol and xanomeline, but not pilocarpine, dose dependently reversed apomorphine-induced disruption of PPI. Thus, xanomeline induced a clear antipsychotic-like effect in PPI, whereas pilocarpine appeared to induce a psychotomimetic-like effect. Xanomeline attenuated amphetamine-induced hyperactivity at doses that had no effect on spontaneous activity, possibly indicating a separation between attenuation of limbic hyperdopaminergic function and the induction of hypolocomotion. Haloperidol and clozapine also reversed amphetamine-induced hyperlocomotion, but at similar doses to those that reduced spontaneous locomotion. Clozapine, but not haloperidol had an anxiolytic-like effect in the CER test. The effects of xanomeline in the CER test were similar to those of clozapine, although at the anxiolytic dose it tended to disrupt baseline levels of lever pressing. Finally, haloperidol, clozapine, pilocarpine, and xanomeline, all induced an increase in dopamine turnover in medial prefrontal cortex. The antipsychotic-like effects of xanomeline in the animal models used here suggest that it may be a useful treatment for psychosis.
影响因子：
--
作者：
N. Swerdlow;D. Braff;N. Taaid;M. Geyer
通讯作者：
N. Swerdlow;D. Braff;N. Taaid;M. Geyer
抗精神病药物对大鼠内侧前额皮质和伏隔核细胞外多巴胺水平的影响。
DOI：
--
发表时间：
1999
期刊：
The Journal of pharmacology and experimental therapeutics.
影响因子：
--
作者：
Kuroki,T;Meltzer,HY;Ichikawa,J
通讯作者：
Ichikawa,J