PAOPA，一种强效 Pro-Leu-甘氨酰胺类似物和多巴胺 D2 受体变构调节剂，可预防 NMDA 受体拮抗剂（MK-801）引起的大鼠社交互动缺陷：对精神分裂症阴性症状治疗的意义。
PAOPA, a potent analogue of Pro-Leu-glycinamide and allosteric modulator of the dopamine D2 receptor, prevents NMDA receptor antagonist (MK-801)-induced deficits in social interaction in the rat: implications for the treatment of negative symptoms in schizophrenia.
机构信息
Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, ON, Canada.
出版信息
Schizophr Res. 2011 Jan;125(1):88-92. doi: 10.1016/j.schres.2010.09.025. Epub 2010 Oct 30.
Abstract
The aim of this study was to investigate whether a potent analogue of the endogenous brain peptide l-prolyl-l-leucyl-glycinamide (PLG), (3(R)-[(2(S)-pyrrolidinylcarbonyl)amino]-2-oxo-1-pyrrolidineacetamide (PAOPA), can prevent the induction of social withdrawal caused by sub-chronic treatment with the non-competitive NMDA (N-methyl-l-aspartate) receptor antagonist, MK-801. Results indicate that MK-801 (0.5 mg/kg) significantly decreased social interaction following sub-chronic treatment (7 days). Treatment with PAOPA (1 mg/kg) blocked the effects of MK-801, and increased the amount of time spent in social interaction in comparison to control animals. These results provide evidence for the development of peptidomimetic compounds for the treatment of social withdrawal and related negative symptoms associated with schizophrenia.
摘要
这项研究的目的是探讨内源性脑肽 l-脯氨酰-l-亮氨酰-甘氨酰胺的一种有效类似物（PLG）（3(R)-[(2(S)-吡咯烷羰基)氨基]-2-氧代-1-吡咯烷乙酰胺（PAOPA））是否可以预防亚慢性给予非竞争性 NMDA（N-甲基-D-天冬氨酸）受体拮抗剂 MK-801 引起的社交回避的诱导。结果表明，MK-801（0.5mg/kg）在亚慢性治疗（7 天）后显著减少社交互动。PAOPA（1mg/kg）治疗阻断了 MK-801 的作用，并与对照动物相比，增加了社交互动的时间。这些结果为开发用于治疗社交回避和与精神分裂症相关的阴性症状的肽模拟化合物提供了证据。
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