Ispronicline
(Synonyms: (2S,4E)-5-(5-异丙基吡啶-3-)-N-甲基戊-4-烯-2-胺,TC-1734; ACD3480) 目录号 : GC63548
Ispronicline (TC-1734) 是一种有效的，具有口服活性的大脑选择性的 α4β2 nAChR 部分激动剂，具有增强记忆的特性和良好的耐受性。Ispronicline 高亲和力与 α4β2 nAChR 结合，Ki= 11 nM。
Cas No.:252870-53-4
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
Ispronicline (TC-1734), an orally active, brain-selective α4β2 nicotine acetylcholine receptor (nAChR) partial agonist, has shown memory-enhancing properties in rodents and a good tolerability profile. Ispronicline binds to the α4β2 nAChR with high affinity (Ki=11 nM) and is highly selective to other nAChRs such as α7 nAChR and α3β4 nAChR[1][2].
Ispronicline (10-20 mg/kg; s.c.) induces c-Fos expression in selective regions of the rat forebrain[1]. Ispronicline pharmacokinetics (half-life of 2 h in rats) contrasts with the long-lasting improvement of working memory (18 h to 2 d)[2].
[1]. Julie Jacobsen, et al. The α4β2 nicotine acetylcholine receptor agonist ispronicline induces c-Fos expression in selective regions of the rat forebrain. Neurosci Lett. 2012 Apr 25;515(1):7-11.
| Cas No. | 252870-53-4 | SDF | |
| 别名 | (2S,4E)-5-(5-异丙基吡啶-3-)-N-甲基戊-4-烯-2-胺,TC-1734; ACD3480 | ||
| 分子式 | C14H22N2O | 分子量 | 234.34 |
| 溶解度 | DMSO : 100 mg/mL (426.73 mM; Need ultrasonic) | 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 | 4.2673 mL | 21.3365 mL | 42.673 mL |
| 5 mM | 0.8535 mL | 4.2673 mL | 8.5346 mL |
| 10 mM | 0.4267 mL | 2.1337 mL | 4.2673 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。
Ispronicline (Targacept)
Curr Opin Investig Drugs 2006 Jan;7(1):60-9.PMID:16425673doi
Targacept (formerly a subsidiary of RJ Reynolds) is developing Ispronicline, the lead in a series of nicotinic acetylcholine (nACh) ligands, as a potential oral treatment for cognitive impairment, including a variety of non-Alzheimer's dementias. In July 2005, Targacept was preparing for a phase II study in patients with mild-to-moderate Alzheimer's disease.
Nicotine-like discriminative and aversive effects of two α4β2-selective nicotine agonists, Ispronicline and metanicotine
Behav Pharmacol 2021 Sep 1;32(6):497-504.PMID:34320519DOI:10.1097/FBP.0000000000000644.
An attempt to determine the receptor selective nature of some of nicotine's behavioral effects was undertaken through the evaluation of the ability of two nicotinic α4β2*-selective receptor agonists to produce nicotine-like effects and modify rates of responding in a discrimination assay and in an aversive stimulus assay. A group of eight rats was trained to discriminate the presence of 1 mg/kg nicotine base. Another group of 4-6 rats was trained to report the aversive effects of nicotine by selecting a lever that produced one food pellet over a second lever that produced two food pellets and an intravenous injection of nicotine. Ispronicline and metanicotine, two α4β2*-selective receptor agonists, increased selection of the nicotine-appropriate lever in a dose-related manner, up to a maximum of approximately 75%. The α4β2*-selective receptor antagonist, dihydro-beta-erythroidine blocked both the discriminative stimulus effects and the rate-suppressing effects of Ispronicline, metanicotine, and small, but not large doses of nicotine. The nonselective antagonist, mecamylamine, antagonized the discriminative stimulus effects of each of the three nicotine agonists as well as the rate-decreasing effects of nicotine and metanicotine. Mecamylamine did not modify the rate-decreasing effects of Ispronicline. Both Ispronicline and metanicotine as well as nicotine were avoided in the drug + food vs. food choice situation. The receptor-selective nature of Ispronicline and metanicotine was hereby confirmed in a behavioral assay, as were earlier reports that the discriminative stimulus effects of relatively small doses of nicotine are likely mediated by activity at the α4β2* nicotine receptor.
Effect of Ispronicline, a neuronal nicotinic acetylcholine receptor partial agonist, in subjects with age associated memory impairment (AAMI)
J Psychopharmacol 2007 Mar;21(2):171-8.PMID:17329297DOI:10.1177/0269881107066855.
Cognitive decline seen in the normal elderly is associated with selective loss of neuronal nicotinic acetylcholine receptors (nAChRs). Nicotine given either by inhalation or transdermally helps cognition, but unacceptable side effects limit its utility. The present study assessed the safety, tolerability and effect on cognition of Ispronicline, a highly selective partial agonist at the 4beta2 nAChR, in elderly subjects (n =76) with age associated memory impairment (AAMI). This double-blind, placebo-controlled cross-over study explored ascending oral doses of Ispronicline in the range 50-150 mg given as a single morning dose for a period of 3 weeks. Pharmacokinetics (PK) were assessed, as well as cognitive function measured by means of the Cognitive Drug Research (CDR) computerized test battery. Ispronicline had a favourable safety profile and was well tolerated at doses below 150 mg. No effect of clinical importance was seen on biochemistry, haematology, urine analysis, vital signs, electrocardiogram (ECG) or Holter monitoring. The most frequent drug induced adverse event was light-headedness (dizziness). A beneficial effect was seen on cognition across the dose range. This was most marked at 50 mg on factors measuring attention and episodic memory. PK analysis indicated a plasma Cmax range of 5-25/35 ng/ml Ispronicline was associated with the most beneficial effect. These early results demonstrate Ispronicline was well tolerated and did not display the side effects typical of nicotine. Ispronicline also had a beneficial effect on cognition in subjects with AAMI. This was seen most strongly in a Cmax range that had been predicted from pre-clinical animal studies.
Ispronicline: a novel alpha4beta2 nicotinic acetylcholine receptor-selective agonist with cognition-enhancing and neuroprotective properties
J Mol Neurosci 2006;30(1-2):19-20.PMID:17192610DOI:10.1385/JMN:30:1:19.
To date, the primary treatments for Alzheimer's disease with proven efficacy have been acetylcholinesterase inhibitors that prevent the hydrolysis of acetylcholine (ACh) in the synaptic cleft, thereby prolonging its activity. Although these agents have some benefit in alleviating cognitive impairment, they have limited clinical utility because of insufficient efficacy and marginal tolerability. Within the last decade, there has been much experimental support for the use of therapeutics that directly target nicotinic ACh receptors (nAChRs) to improve cognitive function and slow neurodegenerative disease progression. These findings have spurred considerable research efforts to develop ligands selective for nAChRs, such as ABT-418 (Arneric et al., 1995), SIB-1553 (Bontempi et al., 2001), TC-2403 (Lippiello et al., 1996), and TC-2559 (Bencherif et al., 2000). There is abundant evidence that nAChR modulators have the potential to alleviate cognitive impairment in demented states. In addition to improving cognitive function, a large body of research implicates a role for nAChRs in neuroprotection, suggesting potential for disease modification. An impact of nAChR agonists on disease progression would provide an advantage over currently available treatments for memory loss. The profile of previous nAChR-targeted clinical candidates has not been adequate to warrant further development owing to poor oral bioavailability, side effects, and/or lack of efficacy. Thus, a challenge in nAChR drug design and development has been the reduction of undesirable effects that result from activity at specific nAChRs in the CNS and PNS, including cardiovascular toxicity, emesis, seizures, and hypothermia.
Cognitive enhancement in man with Ispronicline, a nicotinic partial agonist
J Mol Neurosci 2006;30(1-2):169-72.PMID:17192668DOI:10.1385/JMN:30:1:169.
Cholinergic mechanisms are clearly involved in memory deficits associated with Alzheimer's disease (AD) (Perry et al., 1977). Recently, there has been growing interest in the nicotinic approach to the treatment of AD; however, compounds have failed in the clinic because of a lack of separation between central and peripheral nicotinic effects (Potter et al., 1999). Ispronicline (TC-1734) is an orally active, selective, partial agonist of the central alpha4beta2 neuronal nicotinic acetylcholine receptor (nAChR), with high binding affinity to membrane preparations from rat brain or mammalian cells expressing recombinant human alpha4beta2 receptor (Gatto et al., 2004). Ispronicline has no detectable effects on muscle or ganglionic nAChRs, indicating a marked CNS over PNS selectivity. In animal models Ispronicline potently improved cognitive function. A long duration of memory enhancement was displayed in object recognition and radial arm maze tests. Ispronicline pharmacokinetics (half-life of 2 h in rats) contrasts with the long-lasting improvement of working memory (18 h to 2 d) (Gatto et al., 2004).