生物谷报道:一项临床试验发现,一种以谷氨酸调控的神经传递素为靶标的新药能有效地治疗精神分裂症,新成果发表在9月号的《自然—医学》期刊上。
以前的研究反复显示,谷氨酸调控神经传递素的变异与精神分裂症相关,但一直缺少这种关联性的有力证据。对精神分裂症而言,所有常用的处方安定药均以多巴胺受体为靶标。如今,Sandeep Patil和同事报告:一种特别的谷氨酸受体亚型mGlu2/3是一种选择性激动素,它对精神分裂症患者有安定作用。
在一组双盲、安慰剂控制的试验中,他们试验其新药LY2140023对精神分裂症患者的作用,并将这种新药的疗效与最常用的安定药奥氮平进行了比较,奥氮平是以多巴胺受体为靶标的精神分裂症治疗药物。错觉、幻觉、思维混乱、社交退缩、冷漠和情感迟钝均是精神分裂症患者的主要症状,经过4个星期的治疗后,Patil和同事发现,接受LY2140023治疗的患者在这些方面的表现有明显提高。
目前,多巴胺是治疗精神分裂症的唯一靶标,新研究表明,mGlu2/3受体激动素具有安定特性,可成为精神分裂症治疗的第一个替代靶标。
Figure 1 - Blockade of phencyclidine-induced hyperlocomotion by LY404039, but not by olanzapine, is dependent on expression of Grm2 and Grm3 in mice.
(a,b) LY404039 (10 mg per kg body weight subcutaneously) or saline vehicle (a) or olanzapine (1 mg per kg body weight subcutaneously.) or saline vehicle (b) were administered 30 min before phencyclidine (7.5 mg per kg body weight intraperitoneally) or saline vehicle in either wild-type mice or mice lacking expression of mGlu2/3 receptors, and motor activity (ambulations) was measured for 1 h. Data presented are mean + s.e.m. for each experiment (n = 7–8 animals per group). *P < 0.05 compared to the Vehicle/PCP control group.
原文出处:
Activation of mGlu2/3 receptors as a new approach to treat schizophrenia: a randomized Phase 2 clinical trial
Sandeep T Patil, Lu Zhang, Ferenc Martenyi, Stephen L Lowe, Kimberley A Jackson, Boris V Andreev, Alla S Avedisova, Leonid M Bardenstein, Issak Y Gurovich, Margarita A Morozova, Sergey N Mosolov, Nikolai G Neznanov, Alexander M Reznik, Anatoly B Smulevich, Vladimir A Tochilov, Bryan G Johnson, James A Monn & Darryle D Schoepp
Published online: 02 September 2007; | doi:10.1038/nm1632
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