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].

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].

ABT-239 (3 mg/kg, i.p.) dramatically postpones the onset of seizures, decreases behavioral seizures induced by KA, and lowers the frequency of head bobbing and forelimb clonus in mice. In contrast, a higher dose combination of ABT-239 (3 mg/kg, i.p.) results in enhanced reduction in all stages of immobility, head bobbing, and forelimb clonus. ABT-239 (1 mg/kg, i.p.) and sub-therapeutic dose of SVP (150 mg/kg, i.p.) significantly reduce these symptoms. In mice, the number of pyknotic neurons in the hippocampi is more effectively reduced by ABT-239 (3 mg/kg, i.p.) and TDZD-8 (10 mg/kg, i.p.). The strongest increase in Bcl-2 expression and lowest level of Bax are produced by the high dose combination of ABT-239 and TDZD-8[1]. In WT mice, but not in histamine-depleted mice, ABT-239 (3 mg/kg, i.p.) administration creates long-term memories from short-term learning events[2]. The enhancement of nicotine-induced memory acquisition and consolidation is further enhanced by the concurrent administration of ABT-239 (1 and 3 mg/kg, i.p.) and nicotine (0.035 mg/kg, i.p.) or ABT-239 (0.1 mg/kg, i.p.) and nicotine (0.0175 mg/kg, i.p.)[3].

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In the modified elevated plus maze (mEPM) test in mice, acute administration of ABT-239 alone (0.1-3 mg/kg, i.p.) did not affect memory acquisition or consolidation, as measured by transfer latency (TL).[3]
When co-administered with an active dose of nicotine (0.035 mg/kg, s.c.), ABT-239 (1 and 3 mg/kg, i.p.) significantly potentiated nicotine-induced improvement in both memory acquisition and consolidation, further reducing TL compared to nicotine alone.[3]
When co-administered with a subthreshold dose of nicotine (0.0175 mg/kg, s.c.), a subthreshold dose of ABT-239 (0.1 mg/kg, i.p.) also produced a significant improvement in both memory acquisition and consolidation, an effect not seen with either drug alone at these doses.[3]
At the doses tested (0.1-3 mg/kg, i.p.), ABT-239 alone or in combination with nicotine did not significantly alter locomotor activity in mice, indicating that its effects on memory are not due to non-specific motor stimulation or sedation.[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.

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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 has been reported to have good oral bioavailability and excellent blood-brain barrier penetration. [3]

Within the dose range used in this study (up to 3 mg/kg, intraperitoneal injection), ABT-239 did not cause significant changes in motor activity, indicating a lack of acute, severe neurotoxicity or sedative/excitatory 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/reverse agonist. [3] Studies have shown that the blocking effect of ABT-239 on H₃ receptors can enhance the memory-enhancing effect of nicotine in mice, suggesting an interaction between the histaminergic and nicotinic cholinergic systems in cognitive function. [3] The mechanism may involve ABT-239-mediated regulation of the release of neurotransmitters (e.g., acetylcholine, dopamine) in key memory regions of the brain (e.g., the prefrontal cortex and hippocampus), thereby enhancing the effect of nicotine. [3] Given its potential cognitive-enhancing effect at doses that do not affect cognitive function, ABT-239 is a promising candidate drug for the treatment of cognitive impairment. [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

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

Solubility in Formulation 1: ≥ 2.5 mg/mL (7.57 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: 2.5 mg/mL (7.57 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 2.5 mg/mL (7.57 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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 (Please use freshly prepared in vivo formulations for optimal results.)