Pozanicline
(Synonyms: ABT-089) 目录号 : GC36952
Pozanicline (ABT-089) 是一种新型的胆碱能药物，是 α4β2* nAChRs 部分激动剂，显示对 α6β2* 和 α4α5β2 nAChR 亚型的高选择性。Pozanicline 与 [3H] cytisine位点的结合亲和力 (Ki; rat) 为 16.7 nM。Pozanicline 逆转尼古丁戒断诱导的认知缺陷，可能是尼古丁成瘾的新治疗策略的有效组成部分。
Cas No.:161417-03-4
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Pozanicline (ABT-089) selectively activate neuronal nicotinic acetylcholine receptor (nAChR) subtypes, is a novel cholinergic agent that is a partial agonist at α4β2* nAChRs (Ki=16 nM) and shows high selectivity for α6β2* and α4α5β2 nAChR subtypes, the binding affinity (Ki, rat) for Pozanicline to [3H] cytisine sites is 16.7 nM.Pozanicline reverses nicotine withdrawal-induced cognitive deficits, may be an effective component of novel therapeutic strategies for nicotine addiction[1]. Ki: 16 nM (α4β2* nAChR)[1]
[1]. Sullivan JP, et al. ABT-089 [2-methyl-3-(2-(S)-pyrrolidinylmethoxy)pyridine]: I. A potent and selective cholinergic channel modulator with neuroprotective properties. J Pharmacol Exp Ther. 1997 Oct;283(1):235-46. [2]. Yildirim E, et al. ABT-089, but not ABT-107, ameliorates nicotine withdrawal-induced cognitive deficits in C57BL6/J mice. Behav Pharmacol. 2015 Apr;26(3):241-8.
| Cas No. | 161417-03-4 | SDF | |
| 别名 | ABT-089 | ||
| Canonical SMILES | CC1=C(OC[C@H]2NCCC2)C=CC=N1 | ||
| 分子式 | C11H16N2O | 分子量 | 192.26 |
| 溶解度 | Soluble in DMSO | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 5.2013 mL | 26.0064 mL | 52.0129 mL |
| 5 mM | 1.0403 mL | 5.2013 mL | 10.4026 mL |
| 10 mM | 0.5201 mL | 2.6006 mL | 5.2013 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Pozanicline for the treatment of attention-deficit/hyperactivity disorder
Expert Opin Investig Drugs 2014 Nov;23(11):1585-93.PMID:25196198DOI:10.1517/13543784.2014.956078.
Introduction: Attention-deficit/hyperactivity disorder (ADHD) is the most common neurobehavioral disorder occurring in childhood and often continues into adolescence and adulthood. The pathophysiology of ADHD is complex and likely involves multiple neurotransmitter systems. Medications currently used for the treatment of ADHD enhance dopaminergic and/or noradrenergic transmission. However, none of these drugs target the cholinergic system, which is also thought to play a significant role in cognitive disturbances such as those found in ADHD. Areas covered: In this review, the authors briefly discuss the cholinergic system, including multiple neuronal nicotinic receptor (NNR) subtypes that mediate the positive and negative effects of nicotine, in the context of animal models of ADHD. They also discuss the pharmacology of the NNR Pozanicline , a partial agonist with high in vitro binding affinity and selectivity for the α4β2 NNR subtype. Finally, the authors examine Pozanicline's clinical developments. Expert opinion: Pozanicline was shown to be effective in a pilot study in humans with ADHD, but larger trials were negative. Developing an efficacious therapy is difficult. ADHD is a complex disorder with an unknown cause, and it is unclear, at this time, which qualities from NNR agonists are needed to treat it. It is therefore necessary to develop a more enhanced understanding of the nicotinic cholinergic system and its role in ADHD. Furthermore, new research paradigms may need to be employed to find drugs that are effective in patients with ADHD.
A randomized pilot study of the efficacy and safety of ABT-089, a novel α4β2 neuronal nicotinic receptor agonist, in adults with attention-deficit/hyperactivity disorder
J Clin Psychiatry 2012 Jun;73(6):783-9.PMID:22795204DOI:10.4088/JCP.10m06719.
Objective: ABT-089, an α4β2 neuronal nicotinic receptor partial agonist (generic name Pozanicline), has demonstrated efficacy in adults with attention-deficit/hyperactivity disorder (ADHD) at doses of 40 mg once daily and 40 mg twice daily. The purpose of this exploratory pilot study was to obtain initial safety, tolerability, and efficacy data for an ABT-089 80-mg once-daily regimen to inform a decision of whether to include an 80-mg once-daily dose regimen in subsequent, definitive (phase 3) efficacy studies. Method: This phase 2, randomized, double-blind, parallel-group, placebo-controlled pilot study was conducted at 12 sites from March to August 2008. A screening/washout period of up to 4 weeks was followed by an 8-week double-blind treatment period. Eligible subjects met DSM-IV-TR criteria for ADHD and were randomized in a 1:1:1 ratio to ABT-089 40 mg once daily, ABT-089 80 mg once daily, or placebo. The primary efficacy variable was reduction from baseline to the final evaluation in the investigator-rated Conners' Adult ADHD Rating Scale for each active treatment group versus placebo. Safety assessments and pharmacokinetic sampling were also conducted. Results: A total of 160 subjects were randomized, with 137 (86%) completing the trial. No statistically significant treatment effects were observed with either ABT-089 dose for any efficacy measures. The most commonly reported adverse events in the active treatment groups were nasopharyngitis (6.6%), upper respiratory tract infection (6.6%), and somnolence (5.7%). The incidence of adverse events did not differ significantly between active groups and placebo. There were no clinically significant laboratory, electrocardiogram, or physical examination findings. Conclusions: ABT-089 was generally well tolerated at doses up to 80 mg. Because ABT-089 is a weak partial neuronal nicotinic receptor agonist, the results may not predict the potential efficacy for other, more potent neuronal nicotinic receptor agonists. Trial registration: ClinicalTrials.gov identifier: NCT00640185.