JNJ-16259685

mGluR1 ( IC50 = 19 nM )

JNJ-16259685 有效且完全抑制谷氨酸 (30 μM) 诱导的大鼠 mGlu1a 受体细胞内 Ca2+ 浓度增加，IC50 值为 3.24±1.00 nM。 CPCCOET 和 BAY 36-7620 的 IC50 值分别为 17.8±10.3 μM 和 161±38 nM。 JNJ16259685 阻断谷氨酸 (30 μM) 诱导的人 mGlu1a 受体 Ca2+ 动员的效力为 1.21±0.53 nM (IC50 n=3)。 JNJ16259685 抑制谷氨酸 (3 μM) 诱导的大鼠 mGlu5a 受体细胞内 Ca2+ 浓度升高，IC50 值为 1.31±0.39 μM (n=4)。 JNJ16259685 阻断谷氨酸 (3 μM) 诱导的人 mGlu5 受体上的 Ca2+ 动员，IC50 为 28.3±11.7 μM (n=4)。 JNJ16259685 对任何 I 组 mGlu 受体均不表现出激动剂活性[3]。

相比之下，JNJ-16259685（0.125、0.25、0.5、1、2、4和8 mg/kg，ip）显着减少了挖掘行为（0.25-8 mg/kg）、威胁（所有剂量）和攻击所花费的时间与车辆组[1]。 JNJ16259685 (30 mg/kg) 对运动活动的影响非常小。 JNJ16259685 显着减少饲养行为、探索新环境和按下杠杆以获得食物奖励（大鼠：0.3 mg/kg；小鼠：1 mg/kg）。皮下注射 JNJ16259685 (30 mg/kg) 对小鼠对大声听觉刺激或足部震动的反射性惊吓反应没有影响[2]。 JNJ16259685 在占据大鼠小脑和丘脑中枢 mGlu1 受体方面表现出高效能（ED50 分别=0.040 和 0.014 mg/kg）[3]。

Mice: There are nine mouse groups in use. The animals are randomized into seven experimental groups (N=14–16 each) that receive injections of JNJ16259685 and two control groups (n=15 each) that receive only saline or saline (90%) plus DMSO (10%). In order to provide suitable injection doses, JNJ16259685 is diluted in saline (90%) plus DMSO (10%) and given in seven doses: 0.125, 0.25, 0.5, 1, 2, 4, and 8 mg/kg. The dosages are selected based on the results of recent behavioral research with this substance. Ten milliliters per kilogram of drug or vehicle are injected intraperitoneally.
Rats: The overt behavioral, neurological, and autonomic reactions to the drug challenge are measured using this procedure. In summary, rats are randomly assigned to four groups (n = 6), each of which is given a different dose of JNJ16259685 (0, 3, 10, or 30 mg/kg). The animals are evaluated and scored at 30, 60, 120, and 240 minutes after injection by a skilled observer who is blind to the drugs the animals are receiving. The animals are evaluated for gait, pupil size, body elevation, limb position, limb tone, and passivity. For every behavior, animals that seemed "normal" were given a score of 0, while animals that showed mild, moderate, or severe increases (+) or decreases (−) from normalcy were given scores of ±1, ±2, or ±3. Individual animals are deemed to be significantly affected on the measure if they score ±2 or higher. If three or more of the animals receive a score greater than ±2, the dose is deemed significant.

[1]. JNJ16259685, a selective mGlu1 antagonist, suppresses isolation-induced aggression in male mice. Eur J Pharmacol. 2008 May 31;586(1-3):217-20.

[2]. Characterization of the selective mGluR1 antagonist, JNJ16259685, in rodent models of movement and coordination. Pharmacol Biochem Behav. 2011 Apr;98(2):181-7.

[3]. JNJ16259685, a highly potent, selective and systemically active mGlu1 receptor antagonist. Neuropharmacology. 2004 Dec;47(7):961-72.

[4]. Potent and Specific Action of the mGlu1 Antagonists YM-298198 and JNJ16259685 on Synaptic Transmission in Rat Cerebellar Slices. Br J Pharmacol. 2007 Jul;151(6):870-6.

C20H23NO3

325.41

325.17

C, 73.82; H, 7.12; N, 4.30; O, 14.75

409345-29-5

Solid powder

COC1CCC(CC1)C(=O)C2=CC3=CC4=C(N=C3C=C2)OCCC4

QOTAQTRFJWLFCR-UHFFFAOYSA-N

InChI=1S/C20H23NO3/c1-23-17-7-4-13(5-8-17)19(22)14-6-9-18-16(11-14)12-15-3-2-10-24-20(15)21-18/h6,9,11-13,17H,2-5,7-8,10H2,1H3

3,4-dihydro-2H-pyrano[2,3-b]quinolin-7-yl-(4-methoxycyclohexyl)methanone

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: ≥ 2.75 mg/mL (8.45 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 27.5 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: ≥ 2.75 mg/mL (8.45 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 27.5mg/mL澄清的DMSO储备液加入到900μL 20％SBE-β-CD生理盐水中，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: ≥ 2.75 mg/mL (8.45 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 27.5 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。