Clinica Psiquiatrica Universitaria, Hospital Clinico de la Universidad de Chile, Santiago, Chile.
Curr Pharm Biotechnol. 2012 Jun;13(8):1543-8. doi: 10.2174/138920112800784790.
Cognitive deficits are trait markers in schizophrenia and the improvement of these dysfunctions has been considered as a new frontier of treatment in this disease. A current model for the patophysiology of schizophrenia states that N-methyl-D-aspartate receptor (NMDAR) hypofunction leads to a dysregulation of gamma-amino butyric acid (GABA) fast- spiking interneurons, consequently disinhibiting pyramidal glutamatergic output and disturbing signal-to-noise ratio. In this way, the modulation of the glutamate activity might constitute a highly promising target for future therapeutic interventions of this disease. In the present review, we discuss key regulatory elements for glutamatergic neurotransmission and provide new insights into their potential role in developing pharmacological treatments. Also, we emphasize the role of certain chemical families as potential sources of new lead compounds with affinity for metabotropic glutamate receptors (mGluRs) with cognitive enhancing properties.
认知缺陷是精神分裂症的特征性标志物，改善这些功能障碍被认为是该疾病治疗的新领域。目前的精神分裂症病理生理学模型表明，N-甲基-D-天冬氨酸受体（NMDAR）功能低下导致γ-氨基丁酸（GABA）快速放电中间神经元的失调，从而抑制锥体谷氨酸能输出并扰乱信号噪声比。通过这种方式，谷氨酸活性的调节可能是这种疾病未来治疗干预的一个极具前景的靶点。在本综述中，我们讨论了谷氨酸能神经传递的关键调节因子，并提供了它们在开发药理学治疗方法中的潜在作用的新见解。此外，我们强调了某些化学家族作为具有认知增强特性的代谢型谷氨酸受体（mGluR）的新的潜在配体化合物的潜在来源的作用。
