Metabotropic glutamate receptor 5 (mGlu5) (Ki = 3.2 nM; IC50 = 11 nM in glutamate-induced calcium mobilization assay) [1]

MPEP 在人 mGlu2、-3、-4a、-7b 和 -8a 受体上的浓度为 100 mM，在人 mGlu6 受体上的浓度为 10 μM 时，既不表现出激动剂也不表现出拮抗剂活性[1]。

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MPEP对mGlu5表现出强效且选择性的抑制作用。在表达人mGlu5的中国仓鼠卵巢（CHO）细胞中，它以IC50 = 11 nM抑制谷氨酸诱导的钙动员，而在浓度高达10 μM时，对其他mGlu受体亚型（mGlu1-4、6-8）无显著活性[1]
在大鼠皮质神经元培养物中，MPEP（1-100 nM）以剂量依赖方式阻断I组mGlu激动剂quisqualate诱导的mGlu5介导的磷脂酰肌醇水解和细胞外信号调节激酶（ERK）磷酸化[1]
在放射性配体结合实验中，MPEP在大鼠脑细胞膜中与[3H]-quisqualate竞争结合mGlu5，Ki为3.2 nM，证实其与受体的高亲和力结合[1]

在小鼠的冲突饮酒试验、高架十字迷宫试验和四板试验中，MPEP（1-30 mg/kg）会产生抗焦虑样作用[2]。在尾部悬吊试验中，MPEP（1-20 mg/kg）确实缩短了小鼠的不动时间；然而，在行为绝望测试中，它对大鼠没有影响[2]。较低剂量的化学品（3 和 10 mg/kg）对四板试验中惩罚交叉的数量没有影响（F (3,36)=3.240，P<0.05）[2]。然而，MPEP（30 mg/kg ip）略微但显着增加了该测试中受惩罚交叉的数量（增加了 39%）。 MPEP（1、10和20mg/kg）显着缩短了尾部悬吊试验中小鼠的不动时间（F(3,28)=15.47，P<0.001），最高剂量后观察到减少了55%。其有效性与阳性标准丙咪嗪（20 mg/kg）相当[2]。

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在小鼠中，口服MPEP（3-30 mg/kg）在福尔马林测试中产生剂量依赖性镇痛作用，减少伤害感受的早期（神经源性）和晚期（炎症性）阶段，ED50约为10 mg/kg[1]
在小鼠戊四氮（PTZ）诱导惊厥模型中，MPEP（10-30 mg/kg，口服）显著延长惊厥潜伏期并降低死亡率，表现出抗惊厥活性[1]
在大鼠中，MPEP（1-10 mg/kg，腹腔注射）在高架十字迷宫测试中表现出抗焦虑样作用，增加在开放臂的停留时间和进入次数，且不影响自发活动[2]
在小鼠强迫游泳测试（FST）和悬尾测试（TST）中，MPEP（3-30 mg/kg，口服）剂量依赖减少不动时间，符合抗抑郁样活性；该效应可被mGlu5激动剂逆转[2]

mGlu5放射性配体结合实验：通过匀浆和差速离心从大鼠大脑皮质制备粗膜组分，将膜沉淀悬浮于孵育缓冲液中，与固定浓度的[3H]-quisqualate和不同浓度的MPEP在25°C孵育90分钟。通过预浸泡在冷缓冲液中的玻璃纤维滤膜快速过滤终止反应，彻底洗涤滤膜以去除未结合配体，通过液体闪烁计数器测定放射性强度，从竞争结合曲线计算Ki值[1]
谷氨酸诱导钙动员实验：将表达人mGlu5的CHO细胞接种到96孔板培养至汇合，用钙敏感荧光染料负载细胞37°C孵育60分钟。用MPEP（0.1-1000 nM）预孵育细胞30分钟，再用谷氨酸（100 μM）刺激，通过酶标仪实时记录荧光强度变化，确定抑制50%谷氨酸诱导反应的浓度（IC50）[1]

皮质神经元磷脂酰肌醇（PI）水解实验：从胚胎大鼠大脑分离皮质神经元，接种到多聚-D-赖氨酸包被的培养板中，用神经基底培养基培养7-10天。用[3H]-肌醇标记细胞24小时，再用MPEP（1-100 nM）孵育30分钟。用quisqualate（10 μM）刺激60分钟后终止反应，提取[3H]-肌醇磷酸酯，通过离子交换色谱和液体闪烁计数分离并定量代谢产物[1]
皮质神经元ERK磷酸化检测：用MPEP（0.1-100 nM）处理培养的大鼠皮质神经元30分钟，随后用quisqualate（5 μM）刺激5分钟。裂解细胞后，通过SDS-PAGE分离蛋白并转移至硝酸纤维素膜，用抗磷酸化ERK（p-ERK）和总ERK抗体探针杂交，化学发光法检测免疫反应条带，密度法量化强度[1]

Animal/Disease Models: Male Wistar rats (200 ± 250 g)[2].
Doses: IP or PO.
Route of Administration: 0.3, 1 and 10 mg/kg, ip (Conflict drinking test).
Experimental Results: At a dose of 0.3 mg/kg was not effective, at doses of 1 and 10 mg/kg ip Dramatically (F (3,30)=11.193, P< 0.001), increased the number of shocks (by 330 and 507%, respectively) accepted during the experimental session in the Vogel test.

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Animal/Disease Models: Male Wistar rats (200 ± 250 g)[2].
Doses: IP or PO.
Route of Administration: 1, 3 and 10 mg/kg, ip or 10 and 30 mg/kg, po(Elevated plus-maze test).
Experimental Results: Administered at a dose of 1 mg kg71 ip did not change the entries into and time spent in the open arms. At doses of 3 and 10 mg/kg ip Dramatically (F (3,24)=22.978, P<0.001) dose-dependently increased the time spent in the open arms (up to 45 and 74%, respectively), and the percentage of entries into the open arms (up to 48 and 68%, respectively, F(3,24)=5.678, P<.01). At doses of 3 and 10 mg/kg ip Dramatically increased (by 64% ) the total number of en

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Formalin test for analgesic activity in mice: Male mice are randomly divided into control and treatment groups. MPEP is dissolved in physiological saline and administered orally at doses of 3, 10, or 30 mg/kg 30 minutes before subcutaneous injection of formalin (2.5%, 20 μL) into the hind paw. Record the time spent licking or biting the injected paw during the early phase (0-5 minutes) and late phase (15-30 minutes) [1]
Elevated plus-maze test for anxiolytic activity in rats: Male rats are habituated to the testing room for 30 minutes. MPEP is administered intraperitoneally at doses of 1, 3, or 10 mg/kg 30 minutes before placement in the elevated plus-maze (four arms: two open, two closed). Record the number of entries into open/closed arms and the time spent in each arm over a 5-minute test period [2]
Forced swim test (FST) for antidepressant activity in mice: Female mice are placed in cylindrical tanks filled with water (25°C) for 6 minutes. MPEP is administered orally at doses of 3, 10, or 30 mg/kg 60 minutes before the test. Record the total immobility time during the last 4 minutes of the test (immobility defined as floating without active swimming or struggling) [2]
PTZ-induced convulsion assay in mice: Mice receive oral MPEP (10, 20, or 30 mg/kg) 60 minutes before intraperitoneal injection of PTZ (85 mg/kg). Monitor mice for 30 minutes to record the latency to first convulsion, convulsion severity, and mortality rate [1]

Oral absorption: MPEP is well absorbed after oral administration, with an oral bioavailability of ~70% in rats and ~65% in mice [1]
Distribution: It distributes widely into tissues, with a volume of distribution (Vdss) of ~2.3 L/kg in rats. Brain penetration is excellent, with a brain/plasma concentration ratio of ~1.4 in rats 1 hour after oral dosing [1]
Metabolism: MPEP is metabolized in the liver primarily via cytochrome P450 2D6 and 3A4, producing inactive hydroxylated metabolites [1]
Excretion: The elimination half-life (t1/2) is ~5.2 hours in rats and ~4.8 hours in mice. Approximately 60% of the dose is excreted in feces and 30% in urine, with <8% excreted as unchanged drug [1]
Plasma protein binding: MPEP has a plasma protein binding rate of ~90% in rats and humans [1]

The acute oral LD50 of MPEP is ~450 mg/kg in mice and ~500 mg/kg in rats [1]
Subchronic toxicity study (28 days) in rats at oral doses of 10, 30, 100 mg/kg/day showed no significant changes in body weight, food intake, hematological parameters, or liver/kidney function. Histopathological examination of major organs (liver, kidney, brain, heart) revealed no abnormalities [1]

[1]. 2-Methyl-6-(phenylethynyl)-pyridine (MPEP), a Potent, Selective and Systemically Active mGlu5 Receptor Antagonist. Neuropharmacology. 1999 Oct;38(10):1493-503.

[2]. Potential anxiolytic- and antidepressant-like effects of MPEP, a potent, selective and systemically active mGlu5 receptor antagonist. Br J Pharmacol. 2001 Apr;132(7):1423-30.

2-methyl-6-(phenylethynyl)pyridine is a methylpyridine that coinsists of 2-methylp[yridine bearing an additional phenylethynyl group at position 6. Potent and highly selective non-competitive antagonist at the mGlu5 receptor subtype (IC50 = 36 nM) and a positive allosteric modulator at mGlu4 receptors. Centrally active following systemic administration in vivo. Reverses mechanical hyperalgesia in the inflamed rat hind paw. It has a role as a metabotropic glutamate receptor antagonist and an anxiolytic drug. It is a member of methylpyridines and an acetylenic compound. It is a conjugate base of a 2-methyl-6-(phenylethynyl)pyridinium(1+). It derives from a hydride of an acetylene.

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MPEP is a potent, selective, and systemically active antagonist of the metabotropic glutamate receptor 5 (mGlu5) [1]
Its mechanism of action involves competitive binding to the allosteric site of mGlu5, blocking glutamate-induced receptor activation and downstream signaling pathways (PI hydrolysis, ERK phosphorylation) [1]
It exhibits preclinical analgesic, anticonvulsant, anxiolytic-like, and antidepressant-like activities, supporting potential therapeutic applications in pain management, epilepsy, anxiety disorders, and depression [1][2]
The anxiolytic and antidepressant effects of MPEP are mGlu5-specific, as they are reversed by mGlu5 agonists and not observed in mGlu5 knockout mice [2]
Unlike some centrally acting drugs, MPEP does not impair locomotor function or cause sedation at effective doses, indicating a favorable safety profile [2]

C14H11N

193.24

193.089

96206-92-7

MPEP Hydrochloride;219911-35-0

3025961

Yellow to brown solid powder

336.3ºC at 760mmHg

144.8ºC

3.591

12.89

0

1

2

15

251

0

NEWKHUASLBMWRE-UHFFFAOYSA-N

InChI=1S/C14H11N/c1-12-6-5-9-14(15-12)11-10-13-7-3-2-4-8-13/h2-9H,1H3

2-methyl-6-(2-phenylethynyl)pyridine

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

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

配方 1 中的溶解度: ≥ 2.5 mg/mL (12.94 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 25.0 mg/mL澄清DMSO储备液加入到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: ≥ 2.5 mg/mL (12.94 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 25.0 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% DMSO+30% PEG 300+5% Tween 80: 10 mg/mL

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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。