Toloxatone(MD 69276)   中文名称: 涛洛西酮

Monoamine oxidase A (MAO-A) [1]

- 酶抑制作用：托洛沙酮通过与单胺氧化酶A（MAO-A）的黄素腺嘌呤二核苷酸（FAD）辅因子直接相互作用，表现出可逆抑制活性。分光光度法研究显示其剂量依赖性抑制MAO-A活性，分子轨道计算进一步表征了结合亲和力[1]。

- 分光光度法MAO-A抑制实验：将重组MAO-A与犬尿胺底物共同孵育，加入浓度范围为1 μM至1 mM的托洛沙酮，通过监测340 nm处苯甲醛生成的吸光度变化检测酶活性。反应在pH 7.4的磷酸盐缓冲液中于37°C进行，动力学分析证实为可逆抑制[1]。
- FAD结合研究：采用紫外-可见光谱法分析托洛沙酮与FAD的相互作用。将药物滴定至FAD溶液中，记录吸收光谱变化。分子轨道计算（AM1方法）模拟结合模式，显示氢键和π-π堆积相互作用[1]。

Absorption, Distribution and Excretion
Mainly hepatic 1% of drug is excreted unchanged in the urine
High hepatic excretion rate

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Biological Half-Life
1-3 h

34521 rat LD50 oral 1225 mg/kg BEHAVIORAL: ALTERED SLEEP TIME (INCLUDING CHANGE IN RIGHTING REFLEX); BEHAVIORAL: COMA; LUNGS, THORAX, OR RESPIRATION: OTHER CHANGES Drugs of the Future., 1(569), 1976
34521 mouse LD50 oral 1300 mg/kg BEHAVIORAL: ALTERED SLEEP TIME (INCLUDING CHANGE IN RIGHTING REFLEX); BEHAVIORAL: COMA; LUNGS, THORAX, OR RESPIRATION: OTHER CHANGES Drugs of the Future., 1(569), 1976
34521 mouse LD50 intraperitoneal 650 mg/kg BEHAVIORAL: ALTERED SLEEP TIME (INCLUDING CHANGE IN RIGHTING REFLEX); BEHAVIORAL: COMA; LUNGS, THORAX, OR RESPIRATION: OTHER CHANGES Drugs of the Future., 1(569), 1976

[1]. A reversible monoamine oxidase inhibitor, toloxatone: spectrophotometric and molecular orbital studies of the interaction with flavin adenine dinucleotide (FAD). European Journal of Medicinal Chemistry. 1994, 29(4):269-277.

5-(hydroxymethyl)-3-(3-methylphenyl)-1,3-oxazolidin-2-one is a member of the class of oxazolidinones that is 5-(hydroxymethyl)-1,3-oxazolidin-2-one substituted by a 3-methylphenyl group at position 3. It is a member of toluenes, an oxazolidinone and a primary alcohol.
Toloxatone is an antidepressant agent, the first ever use of which was in France, 1984. It acts as a selective and reversible inhibitor of monoamine oxidase-A (MOA).

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Drug Indication
For the treatment of major depressive disorder.

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Mechanism of Action
This medication is a reversible inhibitor of monoamine oxidase type-A (also known as RIMA). MAO-A can be found in norepinephrinergic and serotonergic neurons and regulates the metabolism of serotonin and catecholamines, allowing for increased circulation in the synaptic cleft. Traditional monoamine oxidase inhibitors irreversibly inhibit monoamine oxidase and therefore, side effects, drug interactions, and food interactions persist as long as 2-3 weeks after discontinuing toloxatone. The elevation of serotonin and norepinephrine levels occurs rapidly after medication administration. However, the therapeutic relief of depressive symptoms requires weeks of daily treatment to observe results. Selective and reversible MAO-A inhibitors are more effective in treating major depression without several of the drug and food interactions associated with traditional monoamine oxidase inhibitors.

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Pharmacodynamics
This drug has been shown to help manage the symptoms of depression by maintaining neuro-synaptic levels of serotonin and catecholamines while regulating their metabolism, which leads to relief of depressive symptoms.

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- Mechanism of action: Toloxatone acts as a reversible MAO-A inhibitor by binding to the FAD cofactor, blocking the enzyme's active site. This prevents oxidation of monoamine neurotransmitters (e.g., serotonin, norepinephrine), increasing their synaptic availability [1].
- Pharmacological classification: Classified as a reversible inhibitor of monoamine oxidase A (RIMA), Toloxatone is used as an antidepressant with a lower risk of hypertensive crises compared to irreversible MAO inhibitors [1].

C11H13NO3

207.229

207.09

C, 63.76; H, 6.32; N, 6.76; O, 23.16

29218-27-7

29218-27-7;

34521

White to off-white solid powder

1.245g/cm3

358.9ºC at 760mmHg

76°

170.9ºC

8.9E-06mmHg at 25°C

1.57

1.377

49.77

1

3

2

15

244

0

CC1=CC(=CC=C1)N2CC(OC2=O)CO

MXUNKHLAEDCYJL-UHFFFAOYSA-N

InChI=1S/C11H13NO3/c1-8-3-2-4-9(5-8)12-6-10(7-13)15-11(12)14/h2-5,10,13H,6-7H2,1H3

5-(Hydroxymethyl)-3-(3-methylphenyl)-2-oxazolidinone

MD 69276; MD-69276; Toloxatone; 29218-27-7; Humoryl; Perenum; Toloxatona; Toloxatonum; Taloxotone; Delalande 69,276; MD69276; Toloxatone; Humoryl Delalande 69276; Perenum.

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

注意： 本产品在运输和储存过程中需避光。

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ~125 mg/mL (~603.19 mM)

配方 1 中的溶解度: ≥ 2.08 mg/mL (10.04 mM) (饱和度未知) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将100 μL 20.8 mg/mL澄清DMSO储备液加入400 μL PEG300中，混匀；然后向上述溶液中加入50 μL Tween-80，混匀；加入450 μL生理盐水定容至1 mL。
*生理盐水的制备：将 0.9 g 氯化钠溶解在 100 mL ddH₂O中，得到澄清溶液。

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配方 2 中的溶解度: ≥ 2.08 mg/mL (10.04 mM) (饱和度未知) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将 100 μL 20.8 mg/mL澄清DMSO储备液加入900 μL 20% SBE-β-CD生理盐水溶液中，混匀。
*20% SBE-β-CD 生理盐水溶液的制备（4°C，1 周）：将 2 g SBE-β-CD 溶解于 10 mL 生理盐水中，得到澄清溶液。

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配方 3 中的溶解度: ≥ 2.08 mg/mL (10.04 mM) (饱和度未知) in 10% DMSO + 90% Corn Oil (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将 100 μL 20.8 mg/mL 澄清 DMSO 储备液加入到 900 μL 玉米油中并混合均匀。

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请根据您的实验动物和给药方式选择适当的溶解配方/方案：
1、请先配制澄清的储备液(如：用DMSO配置50 或 100 mg/mL母液(储备液));
2、取适量母液，按从左到右的顺序依次添加助溶剂，澄清后再加入下一助溶剂。以 下列配方为例说明 (注意此配方只用于说明，并不一定代表此产品 的实际溶解配方):
10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline);
假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀/澄清；向上述体系中加入50 μL Tween-80，混合均匀/澄清；然后继续加入450 μL ddH2O (或 saline)定容至 1 mL；
3、溶剂前显示的百分比是指该溶剂在最终溶液/工作液中的体积所占比例;
4、 如产品在配制过程中出现沉淀/析出，可通过加热(≤50℃)或超声的方式助溶;
5、为保证最佳实验结果，工作液请现配现用！
6、如不确定怎么将母液配置成体内动物实验的工作液，请查看说明书或联系我们;
7、 以上所有助溶剂都可在 Invivochem.cn网站购买。