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A Randomized Trial of the N-Methyl-d-Aspartate Receptor Glycine Site Antagonist Prodrug 4-Chlorokynurenine in Treatment-Resistant Depression.
International Journal of Neuropsychopharmacology ( IF 4.5 ) Pub Date : 2020-03-31 , DOI: 10.1093/ijnp/pyaa025
Lawrence T Park 1 , Bashkim Kadriu 1 , Todd D Gould 2, 3 , Panos Zanos 3 , Deanna Greenstein 1 , Jennifer W Evans 1 , Peixiong Yuan 1 , Cristan A Farmer 1 , Mark Oppenheimer 1 , Jomy M George 4 , Lilian W Adeojo 4 , H Ralph Snodgrass 5 , Mark A Smith 5, 6 , Ioline D Henter 1 , Rodrigo Machado-Vieira 7 , Andrew J Mannes 8 , Carlos A Zarate 1
Affiliation  

Ketamine has rapid-acting antidepressant effects but is associated with psychotomimetic and other adverse effects. A 7-chlorokynurenic acid is a potent and specific glycine site N-methyl-d-aspartate receptor antagonist but crosses the blood-brain barrier inefficiently. Its prodrug, L-4-chlorokynurenine (4-Cl-KYN), exerts acute and sustained antidepressant-like effects in rodents and has no reported psychotomimetic effects in either rodents or healthy volunteers. This study examined whether 4-Cl-KYN has rapid antidepressant effects in individuals with treatment-resistant depression.

中文翻译:

N-甲基-d-天冬氨酸受体甘氨酸位点拮抗剂前药4-氯犬尿氨酸在难治性抑郁症中的随机试验。

氯胺酮具有速效抗抑郁作用,但与拟精神病药和其他不良反应有关。7-氯犬尿酸是一种有效且特异性的甘氨酸位点N-甲基-d-天冬氨酸受体拮抗剂,但不能有效地穿过血脑屏障。其前药 L-4-chlorokynurenine (4-Cl-KYN) 在啮齿动物中发挥急性和持续的抗抑郁样作用,并且在啮齿动物或健康志愿者中均未报告有拟精神病作用。本研究检查了 4-Cl-KYN 是否对难治性抑郁症患者具有快速的抗抑郁作用。
更新日期:2020-03-31
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