A Randomized, Double-Blind, Placebo-Controlled, Single Ascending Dose Study to Evaluate Safety, Tolerability, Pharmacokinetic and Food Effect of BCI-838; and, An Open-Label Minidose Bioavailability Study to Compare Several BCI-632 Pro-drug Candidates in Healthy Male Subjects

This study will evaluate the safety, tolerability and pharmacokinetics of BCI-838, its metabolite BCI-632 and several new pro-drugs in healthy male subjects.

开始日期2011-10-01

申办/合作机构

BrainCells, Inc.

100 项与 MGS-0039 相关的临床结果

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100 项与 MGS-0039 相关的转化医学

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100 项与 MGS-0039 相关的专利（医药）

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项与 MGS-0039 相关的文献（医药）

2016-01-01·Progress in Neuro-Psychopharmacology and Biological Psychiatry2区 · 医学

Role of calcium, glutamate and NMDA in major depression and therapeutic application

2区 · 医学

Review

作者: Kiyhankhadiv, Anna ; Borgwardt, Stefan ; Sollberger, Daniel ; Lang, Undine E ; Deutschenbaur, Lorenz ; Beck, Johannes ; Walter, Marc ; Mühlhauser, Markus ; Hasler, Gregor

Major depression is a common, recurrent mental illness that affects millions of people worldwide. Recently, a unique fast neuroprotective and antidepressant treatment effect has been observed by ketamine, which acts via the glutamatergic system. Hence, a steady accumulation of evidence supporting a role for the excitatory amino acid neurotransmitter (EAA) glutamate in the treatment of depression has been observed in the last years. Emerging evidence indicates that N-methyl-D-aspartate (NMDA), group 1 metabotropic glutamate receptor antagonists and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) agonists have antidepressant properties. Indeed, treatment with NMDA receptor antagonists has shown the ability to sprout new synaptic connections and reverse stress-induced neuronal changes. Based on glutamatergic signaling, a number of therapeutic drugs might gain interest in the future. Several compounds such as ketamine, memantine, amantadine, tianeptine, pioglitazone, riluzole, lamotrigine, AZD6765, magnesium, zinc, guanosine, adenosine aniracetam, traxoprodil (CP-101,606), MK-0657, GLYX-13, NRX-1047, Ro25-6981, LY392098, LY341495, D-cycloserine, D-serine, dextromethorphan, sarcosine, scopolamine, pomaglumetad methionil, LY2140023, LY404039, MGS0039, MPEP, 1-aminocyclopropanecarboxylic acid, all of which target this system, have already been brought up, some of them recently. Drugs targeting the glutamatergic system might open up a promising new territory for the development of drugs to meet the needs of patients with major depression.

2014-11-01·Molecular Psychiatry1区 · 医学

Proneurogenic Group II mGluR antagonist improves learning and reduces anxiety in Alzheimer Aβ oligomer mouse

1区 · 医学

Article

作者: Steele, J W ; Carter, T A ; Wedel, P ; Ehrlich, M E ; Barlow, C ; Clemenson, G D ; Lee, S W ; Treuner, K ; Glabe, C ; Gandy, S ; Gadient, R ; Kim, S H ; Gage, F H

Proneurogenic compounds have recently shown promise in some mouse models of Alzheimer's pathology. Antagonists at Group II metabotropic glutamate receptors (Group II mGluR: mGlu2, mGlu3) are reported to stimulate neurogenesis. Agonists at those receptors trigger γ-secretase-inhibitor-sensitive biogenesis of Aβ42 peptides from isolated synaptic terminals, which is selectively suppressed by antagonist pretreatment. We have assessed the therapeutic potential of chronic pharmacological inhibition of Group II mGluR in Dutch APP (Alzheimer's amyloid precursor protein E693Q) transgenic mice that accumulate Dutch amyloid-β (Aβ) oligomers but never develop Aβ plaques. BCI-838 is a clinically well-tolerated, orally bioavailable, investigational prodrug that delivers to the brain BCI-632, the active Group II mGluR antagonist metabolite. Dutch Aβ-oligomer-forming APP transgenic mice (APP E693Q) were dosed with BCI-838 for 3 months. Chronic treatment with BCI-838 was associated with reversal of transgene-related amnestic behavior, reduction in anxiety, reduction in levels of brain Aβ monomers and oligomers, and stimulation of hippocampal neurogenesis. Group II mGluR inhibition may offer a unique package of relevant properties as an Alzheimer's disease therapeutic or prophylactic by providing both attenuation of neuropathology and stimulation of repair.

2013-02-01·Neuropharmacology2区 · 医学

Metabotropic glutamate 2/3 receptor antagonists improve behavioral and prefrontal dopaminergic alterations in the chronic corticosterone-induced depression model in mice

2区 · 医学

Article

作者: Akemichi Baba ; Hirotaka Onoe ; Toshiyuki Kawasaki ; Toshio Matsuda ; Hitoshi Hashimoto ; Shigeyuki Chaki ; Yuki Kita ; Ryota Araki ; Kazuhiro Takuma ; Koji Yano ; Naoki Hiramatsu ; Yukio Ago ; Atsuro Nakazato

Metabotropic glutamate 2/3 (mGlu2/3) receptor antagonists have an antidepressant-like effect, but the exact mechanism still remains unclear. This study examined the effects of mGlu2/3 receptor antagonists in chronic corticosterone-treated mice which could be used as an animal model of depression. In the forced swim test, the mGlu2/3 receptor antagonists MGS0039 (1.0 mg/kg, i.p.) and LY341495 (0.3 mg/kg, i.p) significantly reduced the increased immobility time of mice pretreated with corticosterone (20 mg/kg, s.c.) for 21 days, while desipramine (30 mg/kg, i.p.) and fluoxetine (30 mg/kg, i.p.) did not. The antidepressant-like effect of LY341495 was not blocked by the α-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptor antagonist NBQX (10 mg/kg, i.p.). Systemic administration of LY341495 did not affect basal release of glutamate, dopamine or serotonin in the prefrontal cortex of the control or chronic corticosterone-treated mice. Chronic corticosterone markedly enhanced high K(+)-induced release of dopamine, but not serotonin or glutamate, in the prefrontal cortex. This neurochemical change was blocked by systemic administration of MGS0039 and LY341495, but not desipramine or fluoxetine. These results suggest that chronic corticosterone-treated mice could be used as an animal model of treatment-resistant depression. This study also suggests that the prefrontal dopaminergic system is involved in the antidepressant-like effect of mGlu2/3 receptor antagonists in the chronic corticosterone-induced depression model.

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适应症	最高研发状态	国家/地区	公司	日期
焦虑症	临床1期	-	BrainCells, Inc.	-
焦虑症	临床1期	-	Taisho Pharmaceutical Holdings Co., Ltd.	-
认知障碍	临床1期	-	BrainCells, Inc.	-
认知障碍	临床1期	-	Taisho Pharmaceutical Holdings Co., Ltd.	-
抑郁症	临床1期	-	BrainCells, Inc.	-
抑郁症	临床1期	-	Taisho Pharmaceutical Holdings Co., Ltd.	-
重度抑郁症	临床1期	美国	BrainCells, Inc.	-