Brain Science Institute, Johns Hopkins University, Baltimore, MD 21205, USA.
Curr Pharm Des. 2011;17(2):103-11. doi: 10.2174/138161211795049633.
D-amino acid oxidase (DAAO) catalyzes the oxidative metabolism of D-amino acids including D-serine, a full agonist at the allosteric glycine binding site of the NMDA receptor. D-serine was reported to improve negative and cognitive symptoms of schizophrenia, symptoms poorly addressed by the standard D2 antagonist therapies. Therefore, inhibition of DAAO has gained substantial interest as an effective way to increase D-serine levels in the brain. During the last several years, a growing number of structurally diverse DAAO inhibitors have been identified with significantly higher inhibitory potency compared to the conventional DAAO inhibitors. Some of these new generation of DAAO inhibitors are being evaluated for their ability to enhance D-serine levels in rodents and efficacy in animal models of schizophrenia. This article highlights the progress that has been made toward the discovery of DAAO inhibitors and recent efforts to exploit their therapeutic utility in schizophrenia.
D-氨基酸氧化酶（DAAO）催化 D-氨基酸的氧化代谢，包括 D-丝氨酸，它是 NMDA 受体变构甘氨酸结合位点的全激动剂。有报道称 D-丝氨酸可改善精神分裂症的阴性和认知症状，而这些症状是标准的 D2 拮抗剂疗法难以解决的。因此，抑制 DAAO 作为一种有效增加大脑中 D-丝氨酸水平的方法引起了广泛关注。在过去的几年中，已经发现了越来越多结构多样的 DAAO 抑制剂，与传统的 DAAO 抑制剂相比，它们具有更高的抑制效力。其中一些新一代的 DAAO 抑制剂正在评估其在增强啮齿动物 D-丝氨酸水平和精神分裂症动物模型疗效方面的能力。本文重点介绍了在发现 DAAO 抑制剂方面取得的进展，以及最近在精神分裂症中利用其治疗效用的努力。
