ABT-239

H₃ receptor
ABT-239 (10 μM) perfusion of the TMN increases the release of histamine from the TMN, NBM, and cortex, but not from the striatum or NAcc. In the NBM and cortex, TMN perfusion combined with ABT-239 selectively activates c-Fos[4].

用 ABT-239 (10 μM) 灌注 TMN 会增加 TMN、NBM 和皮质的组胺释放，但不会增加纹状体或 NAcc 的组胺释放。 TMN 灌注 ABT-239 可选择性激活 NBM 和皮质中的 c-Fos[4]。

ABT-239（3 mg/kg，腹腔注射）可显着延迟小鼠癫痫发作，减少 KA 引起的行为性癫痫发作，并减少小鼠头部摆动和前肢阵挛的发生率。 ABT-239（1 mg/kg，腹腔注射）与亚治疗剂量的 SVP（150 mg/kg，腹腔注射）联合使用，可显着减少不动、头部摆动和前肢阵挛的次数，而较高剂量的 ABT 组合-239（3 mg/kg，腹腔注射）导致所有阶段的还原增强。 ABT-239 (3 mg/kg, ip) 和 TDZD-8 (10 mg/kg, ip) 对小鼠海马中固缩神经元的数量有更强大的减少作用。 ABT-239 和 TDZD-8 的高剂量组合可显着增加 Bcl-2 表达以及降低 Bax 水平[1]。在 WT 中，ABT-239（3 mg/kg，腹腔注射）给药可将短期学习事件转化为长期记忆的经历，但在组胺耗尽的小鼠中则不然[2]。同时给予 ABT-239（1 和 3 mg/kg，腹腔注射）和尼古丁（0.035 mg/kg，腹腔注射），或 ABT-239（0.1 mg/kg，腹腔注射）和尼古丁（0.0175 mg/kg，腹腔注射）进一步增强尼古丁诱导的记忆获取和巩固的改善[3]。

---

在小鼠改良高架十字迷宫（mEPM）测试中，单独急性给予 ABT-239（0.1-3 mg/kg，腹腔注射）不影响记忆获取或巩固（以转移潜伏期 TL 衡量）。[3]
当与有效剂量的尼古丁（0.035 mg/kg，皮下注射）合用时，ABT-239（1 和 3 mg/kg，腹腔注射）能显著增强尼古丁诱导的记忆获取和巩固改善，与单独使用尼古丁相比，TL 进一步缩短。[3]
当与阈下剂量的尼古丁（0.0175 mg/kg，皮下注射）合用时，阈下剂量的 ABT-239（0.1 mg/kg，腹腔注射）也能在记忆获取和巩固中产生显著改善，而在此剂量下，两种药物单独使用均无效。[3]
在测试剂量下（0.1-3 mg/kg，腹腔注射），ABT-239 单独或与尼古丁联用均未显著改变小鼠的自发活动，表明其对记忆的影响并非源于非特异性运动刺激或镇静作用。[3]

ABT-239, SVP, and KA solutions are made in pyrogen-free normal saline for injection; TDZD-8, on the other hand, is dissolved in 10% DMSO and injected intraperitoneally in a volume not to exceed 10 mL/kg. There are ten groupings of animals. In a range finding study, animals in the second group (VEH) receive KA at a dose of 10 mg/kg, i.p. (pH 7.2±1), while the first group (CTRL) receives only vehicle (0.9% sodium chloride). This dose causes low-grade seizures (stages 0-4) in all animals without causing any mortality. In most studies, the KA dose used to elicit SE in mice ranged from 6–20 mg/kg to 25–45 mg/kg and higher. Two groups of animals receive increasing doses of ABT-239 (30 min before KA challenge): 1 mg/kg (AL) and 3 mg/kg (AH). In mice with Alzheimer's disease, these doses of ABT-239, which range from 0.1 to 3 mg/kg, show improved cognitive functions as well as disease-modifying properties. Prior to the KA injection, 30 minutes are spent giving the fifth and sixth groups graduated doses of SVP at 150 (SL) and 300 mg/kg (SH). The subeffective dose (the highest dose at which no protection is possible) of SVP at 150 mg/kg combined with ABT-239 at 1 (SLAL) and 3 mg/kg (SLAH), respectively, is given to the seventh and eighth groups. Thirty minutes later, KA administers the combination. Before being exposed to KA, the remaining two groups receive low doses of ABT-239 and TDZD-8, respectively, at 1 and 5 mg/kg (ALTL) and high doses, at 3 and 10 mg/kg (AHTH). The TDZD-8 dosages selected are based on earlier research in which doses between 1 and 10 mg/kg improved psychiatric conditions and decreased inflammation and tissue damage.

---

For memory testing in the modified elevated plus maze (mEPM), male Swiss mice were used.[3]
ABT-239 was suspended in one drop of a 1% Tween 80 solution and then dissolved in saline. This vehicle solution also served as the control.[3]
ABT-239 was administered intraperitoneally (i.p.) at a volume of 10 ml/kg.[3]
To assess effects on memory acquisition, ABT-239 (0.1, 0.3, 1, 3 mg/kg) or vehicle was administered 60 minutes before the first (acquisition) trial of the mEPM test. Memory was assessed 24 hours later during the retention trial without further drug administration.[3]
To assess effects on memory consolidation, ABT-239 (0.1, 0.3, 1, 3 mg/kg) or vehicle was administered intraperitoneally immediately after the first (acquisition) trial. Memory was assessed 24 hours later during the retention trial.[3]
For combination studies with nicotine, ABT-239 (0.1, 1, or 3 mg/kg) or vehicle was administered intraperitoneally 30 minutes before subcutaneous nicotine injection (0.0175 or 0.035 mg/kg). The first mEPM trial was conducted 30 minutes after nicotine injection for acquisition studies.[3]
For consolidation combination studies, ABT-239 or vehicle was administered 30 minutes before nicotine, which was injected immediately after the first trial.[3]
For locomotor activity assessment, mice were injected with ABT-239 or vehicle 30 minutes before nicotine or vehicle and immediately placed in activity chambers for a 60-minute recording session.[3]

ABT-239 is reported to have good oral bioavailability and excellent blood-brain barrier penetration.[3]

At the doses used in this study (up to 3 mg/kg, i.p.), ABT-239 did not induce significant changes in locomotor activity, suggesting a lack of acute, gross neurological toxicity or sedative/stimulant side effects at these doses.[3]

[1]. Histamine H3 receptor antagonism by ABT-239 attenuates kainic acid induced excitotoxicity in mice. Brain Res. 2014 Sep 18;1581:129-40.

[2]. Donepezil, an acetylcholine esterase inhibitor, and ABT-239, a histamine H3 receptor antagonist/inverse agonist, require the integrity of brain histamine system to exert biochemical and procognitive effects in the mouse. Neuropharmacolo.

[3]. Kruk M, e tal. Effects of the histamine H2 receptor antagonist ABT-239 on cognition and nicotine-induced memory enhancement in mice. Pharmacol Rep. 2012;64(6):1316-25.

[4]. Selective brain region activation by histamine H2 receptor antagonist/inverse agonist ABT-239 enhances acetylcholine and histamine release and increases c-Fos expression. Neuropharmacology. 2013 Jul;70:131-40.

ABT-239 is a novel, non-imidazole histamine H₃ receptor antagonist/inverse agonist.[3]
The study suggests that blockade of H₃ receptors by ABT-239 can potentiate the memory-enhancing effects of nicotine in mice, indicating an interaction between histaminergic and nicotinic cholinergic systems in cognition.[3]
The mechanism may involve ABT-239-mediated modulation of neurotransmitter release (e.g., acetylcholine, dopamine) in brain regions critical for memory, such as the prefrontal cortex and hippocampus, which complements nicotine's action.[3]
ABT-239 represents a candidate for the treatment of cognitive disorders due to its potential cognition-enhancing properties at doses that do not disrupt locomotion.[3]

C22H22N2O

330.42288

330.173

C, 79.97; H, 6.71; N, 8.48; O, 4.84

460746-46-7

9818903

Light yellow to khaki solid powder

4.936

40.17

0

3

4

25

490

1

C[C@H]1N(CCC2=CC3=C(C=CC(C4=CC=C(C#N)C=C4)=C3)O2)CCC1

KFHYZKCRXNRKRC-MRXNPFEDSA-N

InChI=1S/C22H22N2O/c1-16-3-2-11-24(16)12-10-21-14-20-13-19(8-9-22(20)25-21)18-6-4-17(15-23)5-7-18/h4-9,13-14,16H,2-3,10-12H2,1H3/t16-/m1/s1

4-[2-[2-[(2R)-2-methylpyrrolidin-1-yl]ethyl]-1-benzofuran-5-yl]benzonitrile

ABT-239; ABT 239; ABT239

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)

DMSO: ≥ 100 mg/mL (~302.7 mM)
H2O: < 0.1 mg/mL

配方 1 中的溶解度: ≥ 2.5 mg/mL (7.57 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。

---

配方 2 中的溶解度: 2.5 mg/mL (7.57 mM) 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), 悬浊液; 超声助溶。
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。

---

View More

配方 3 中的溶解度: ≥ 2.5 mg/mL (7.57 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 25.0 mg/mL 澄清 DMSO 储备液加入到 900 μL 玉米油中并混合均匀。

---

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。