D-Amino Acid Oxidase Inhibitor
(Synonyms: 4H-噻唑[3,2-B]吡咯-5-甲酸) 目录号 : GC43373
An inhibitor of DAAO
Cas No.:39793-31-2
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
D-Amino acid oxidase inhibitor is an inhibitor of D-amino acid oxidase (DAAO) with IC50 values of 145 and 114 nM in CHO cells expressing human and rat DAAO, respectively. It is selective for DAAO over a panel of 150 enzymes, receptors, and ion channels when used at a concentration of 30 μM. D-Amino acid oxidase inhibitor (10-200 mg/kg, i.p.) inhibits DAAO activity in rat kidney and cerebellum in a dose- and time-dependent manner. It increases levels of D-serine in rat plasma and cerebral spinal fluid (CSF) but has no effect on hyperlocomotion or dopamine efflux in the nucleus accumbens induced by amphetamine in rats. DAAO inhibitor reduces formalin-induced paw flinching in rats (EC50 = 0.17 μg per animal) indicating an antinociceptive effect.
| Cas No. | 39793-31-2 | SDF | |
| 别名 | 4H-噻唑[3,2-B]吡咯-5-甲酸 | ||
| Canonical SMILES | OC(C1=CC(SC=C2)=C2N1)=O | ||
| 分子式 | C7H5NO2S | 分子量 | 167.2 |
| 溶解度 | DMF: 30 mg/ml,DMSO: 30 mg/ml,DMSO:PBS (pH 7.2) (1:2): 0.3 mg/ml,Ethanol: 2 mg/ml | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 5.9809 mL | 29.9043 mL | 59.8086 mL |
| 5 mM | 1.1962 mL | 5.9809 mL | 11.9617 mL |
| 10 mM | 0.5981 mL | 2.9904 mL | 5.9809 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Efficacy and safety of add-on sodium benzoate, a D-Amino Acid Oxidase Inhibitor, in treatment of schizophrenia: A systematic review and meta-analysis
Asian J Psychiatr 2022 Feb;68:102947.PMID:34890931DOI:10.1016/j.ajp.2021.102947.
Background: The role of sodium benzoate, an NMDA receptor enhancer, in schizophrenia has been evaluated in a few clinical trials, but results are contradictory and inconclusive. The present meta-analysis has evaluated the efficacy and safety of add-on sodium benzoate for the treatment of schizophrenia. Methods: After performing a literature search on MEDLINE/PubMed, Scopus, Cochrane databases and International Clinical Trial Registry Platform, reviewers assessed eligibility and extracted data from four relevant articles. PRISMA guidelines were followed in the selection, analysis, and reporting of findings. The random-effect model was used to estimate effect size. Quality assessment was done using the risk of bias assessment tool, and sensitivity analysis was done in case of high heterogeneity. Results: Add-on sodium benzoate can improve positive symptoms of schizophrenia significantly (MD: -1.87; 95%CI: -3.25 to -0.48; p = 0.008) but had no significant favourable effect on negative symptoms (p = 0.84), general psychopathology (p = 0.49), and total PANSS score (p = 0.19) over the control. There was no significant improvement in GAF (p = 0.43), CGI (p = 0.58), cognitive function (p = 0.46) and quality of life (p = 0.73). Extrapyramidal symptoms were significantly higher (MD: 0.39; 95% CI:0.19-0.60; p = 0.0002) in the sodium benzoate group in comparison to the control group; however, there was no significant difference in respect to other adverse events. Conclusion: Sodium benzoate can improve the positive symptoms of schizophrenia without any beneficial effect on other symptomatology, cognition, quality of life and functioning. Further studies are needed to evaluate long-term efficacy, safety and use in specific subgroups of patients.
Effects of Sodium Benzoate, a D-Amino Acid Oxidase Inhibitor, on Perceived Stress and Cognitive Function Among Patients With Late-Life Depression: A Randomized, Double-Blind, Sertraline- and Placebo-Controlled Trial
Int J Neuropsychopharmacol 2022 Aug 4;25(7):545-555.PMID:35023557DOI:10.1093/ijnp/pyac006.
Background: Compared with adults with depression in the general population, elderly depressive patients are prone to poor treatment response, more side effects, and early withdrawal with current antidepressants (which principally modulate monoamines). Whether N-methyl-D-aspartate receptor enhancement can benefit treatment of late-life depression deserves study. This study aims to compare sodium benzoate (a D-Amino Acid Oxidase Inhibitor and an indirect N-methyl-D-aspartate receptor enhancer), sertraline (a selective serotonin reuptake inhibitor), and placebo in the treatment of late-life depression. Methods: In this randomized, double-blind trial, 117 patients with major depressive disorder aged 55 years or older received 8-week treatment of 250-1500 mg/d of sodium benzoate, 25-150 mg/d of sertraline, or placebo in 2 medical centers. The primary outcome measures were Hamilton Depression Rating Scale and Perceived Stress Scale scores. Results: Three treatments similarly decreased clinicians-rated Hamilton Depression Rating Scale scores. Compared with placebo, sodium benzoate but not sertraline substantially improved Perceived Stress Scale scores and cognitive function. Sertraline, but not benzoate, significantly reduced self-report Geriatric Depression Scale scores. Benzoate and placebo showed similar safety profiles, while sertraline was more likely to raise low-density lipoprotein than benzoate and placebo. Benzoate-treated patients were less likely to drop out than sertraline or placebo recipients. Conclusions: Sertraline can reduce subjective depressive symptoms, while benzoate can decrease perceived stress, improve cognitive function, and enhance treatment adherence in late-life depression patients. The results show promise for D-amino acid oxidase inhibition as a novel approach for perceived stress and cognitive decline among patients with late-life depression. Trial registration: ClinicalTrials.gov Identifier: NCT03414931. Registered January 2016.
Role of d-amino acid oxidase in the production of kynurenine pathway metabolites from d-tryptophan in mice
J Neurochem 2016 Feb;136(4):804-814.PMID:26661897DOI:10.1111/jnc.13455.
The kynurenine pathway (KP), the major catabolic route of the essential amino acid l-tryptophan (l-TRP), contains several neuroactive compounds, including kynurenic acid, 3-hydroxykynurenine (3-HK), and quinolinic acid (QUIN). The role of the d-enantiomer (d-TRP) in KP metabolism has received little attention so far. d-TRP can be converted to l-TRP by d-amino acid oxidase, and the same enzyme can produce d-kynurenine, a known bioprecursor of KYNA. To analyze these complex metabolic events systematically in vivo, we injected mice with d-TRP (300 mg/kg, i.p.) and examined KP metabolism in the absence or presence of the D-Amino Acid Oxidase Inhibitor 3-methylpyrazole-5-carboxylic acid (MPC; 100 mg/kg, i.p.,). After 90 min, newly formed l-TRP was recovered in plasma, liver, forebrain, and cerebellum, and MPC prevented its neosynthesis in all tissues. In the same animals, de novo production of d-kynurenine from d-TRP was also observed, but was much higher in the periphery than in the brain. d-TRP administration raised KYNA, 3-HK, and QUIN levels in all tissues examined, and KYNA production from d-TRP was significantly reduced after pre-treatment with MPC. These results indicate that catabolic routes other than those classically ascribed to l-TRP and l-kynurenine can account for the synthesis of KYNA, 3-HK and QUINin vivo. The essential amino acid l-tryptophan is catabolized via the kynurenine pathway (KP). We explored the role of the d-enantiomer in KP metabolism in mice in vivo. We report that d-tryptophan is metabolized in both brain and periphery and converted to KP metabolites, including d-kynurenine and l-kynurenine, kynurenic acid, 3-hydroxykynurenine, and quinolinic acid. Pharmacological experiments confirm the involvement of d-amino acid oxidase in these processes. Our results indicate that this enzyme participates in the synthesis of KP metabolites from d-tryptophan.
Sodium Benzoate, a D-Amino Acid Oxidase Inhibitor, Added to Clozapine for the Treatment of Schizophrenia: A Randomized, Double-Blind, Placebo-Controlled Trial
Biol Psychiatry 2018 Sep 15;84(6):422-432.PMID:29397899DOI:10.1016/j.biopsych.2017.12.006.
Background: Clozapine is the last-line antipsychotic agent for refractory schizophrenia. To date, there is no convincing evidence for augmentation on clozapine. Activation of N-methyl-D-aspartate receptors, including inhibition of D-amino acid oxidase that may metabolize D-amino acids, has been reported to be beneficial for patients receiving antipsychotics other than clozapine. This study aimed to examine the efficacy and safety of a D-Amino Acid Oxidase Inhibitor, sodium benzoate, for schizophrenia patients who had poor response to clozapine. Methods: We conducted a randomized, double-blind, placebo-controlled trial. Sixty schizophrenia inpatients that had been stabilized with clozapine were allocated into three groups for 6 weeks' add-on treatment of 1 g/day sodium benzoate, 2 g/day sodium benzoate, or placebo. The primary outcome measures were Positive and Negative Syndrome Scale (PANSS) total score, Scale for the Assessment of Negative Symptoms, Quality of Life Scale, and Global Assessment of Functioning. Side effects and cognitive functions were also measured. Results: Both doses of sodium benzoate produced better improvement than placebo in the Scale for the Assessment of Negative Symptoms. The 2 g/day sodium benzoate also produced better improvement than placebo in PANSS-total score, PANSS-positive score, and Quality of Life Scale. Sodium benzoate was well tolerated without evident side effects. The changes of catalase, an antioxidant, were different among the three groups and correlated with the improvement of PANSS-total score and PANSS-positive score in the sodium benzoate group. Conclusions: Sodium benzoate adjuvant therapy improved symptomatology of patients with clozapine-resistant schizophrenia. Further studies are warranted to elucidate the optimal dose and treatment duration as well as the mechanisms of sodium benzoate for clozapine-resistant schizophrenia.
The D-Amino Acid Oxidase Inhibitor luvadaxistat improves mismatch negativity in patients with schizophrenia in a randomized trial
Neuropsychopharmacology 2023 Mar 16;1-8.PMID:36928351DOI:10.1038/s41386-023-01560-0.
Several attempts have been made to enhance N-methyl-D-aspartate (NMDA) receptor function in schizophrenia, but they have yielded mixed results. Luvadaxistat, a D-amino acid oxidase (DAAO) inhibitor that increases the glutamate co-agonist D-serine levels, is being developed for the treatment of cognitive impairment associated with schizophrenia. We conducted a biomarker study in patients, assessing several endpoints related to physiological outcomes of NMDA receptor modulation to determine whether luvadaxistat affects neural circuitry biomarkers relevant to NMDA receptor function and schizophrenia. This was a randomized, placebo-controlled, double-blind, two-period crossover phase 2a study assessing luvadaxistat 50 mg and 500 mg for 8 days in 31 patients with schizophrenia. There were no treatment effects of luvadaxistat at either dose in eyeblink conditioning, a cerebellar-dependent learning measure, compared with placebo. We observed a nominally significant improvement in mismatch negativity (MMN) and a statistical trend to improvement for auditory steady-state response at 40 Hz, in both cases with 50 mg, but not with 500 mg, compared with placebo. Although the data should be interpreted cautiously owing to the small sample size, they suggest that luvadaxistat can improve an illness-related circuitry biomarker at doses associated with partial DAAO inhibition. These results are consistent with 50 mg, but not higher doses, showing a signal of efficacy in cognitive endpoints in a larger phase 2, 12-week study conducted in parallel. Thus, MMN responses after a short treatment period may predict cognitive function improvement. MMN and ASSR should be considered as biomarkers in early trials addressing NMDA receptor hypofunction.