Idalopirdine
(Synonyms: Lu AE58054) 目录号 : GC36291
A 5-HT6 receptor antagonist
Cas No.:467459-31-0
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
LU AE58054 is an antagonist of the serotonin (5-HT) receptor subtype 5-HT6 (Ki = 0.83 nM).1 It is selective for 5-HT6 over other 5-HT receptor subtypes (Kis = 250 to >10,000 nM) and 70 other targets but does bind to α1A- and α1B-adrenergic receptors (α1B-ARs; Kis = 21 and 22 nM, respectively). LU AE58054 (5-20 mg/kg) reverses phencyclidine-induced deficits in novel object recognition memory in rats. When administered in combination with the cholinesterase inhibitor rivastigmine , LU AE58054 has an additive effect on the decreased number of slips and falls made by rats with bilateral striatal-dopaminergic and cortical-cholinergic system lesions, a model of Parkinson’s disease motor disruption, in the Michigan complex motor control task.2
1.Arnt, J., Bang-Andersen, B., Grayson, B., et al.Lu AE58054, a 5-HT6 antagonist, reverses cognitive impairment induced by subchronic phencyclidine in a novel object recognition test in ratsInt. J. Neuropsychopharmacol.13(8)1021-1033(2010) 2.Cherian, A.K., Kucinski, A., Wu, R., et al.Co-treatment with rivastigmine and idalopirdine reduces the propensity for falls in a rat model of falls in Parkinson's diseasePsychopharmacology (Berl)236(6)1701-1715(2019)
| Cas No. | 467459-31-0 | SDF | |
| 别名 | Lu AE58054 | ||
| Canonical SMILES | FC1=CC(NC=C2CCNCC3=CC(OCC(F)(C(F)F)F)=CC=C3)=C2C=C1 | ||
| 分子式 | C20H19F5N2O | 分子量 | 398.37 |
| 溶解度 | DMF: 30 mg/ml,DMSO: 30 mg/ml,Ethanol: 30 mg/ml | 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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| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.5102 mL | 12.5511 mL | 25.1023 mL |
| 5 mM | 0.502 mL | 2.5102 mL | 5.0205 mL |
| 10 mM | 0.251 mL | 1.2551 mL | 2.5102 mL |
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| 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 |
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| % DMSO % % Tween 80 % saline | ||||||||||
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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，
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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。
Idalopirdine as a treatment for Alzheimer's disease
Expert Opin Investig Drugs 2015;24(7):981-7.PMID:26022777DOI:10.1517/13543784.2015.1052402.
Introduction: Alzheimer's disease (AD) is the most common cause of dementia in the elderly. Pharmacological treatment of AD involves acetylcholinesterase inhibitors (AChEIs) for mild-to-moderate AD and memantine for severe AD. These drugs provide mainly symptomatic short-term benefits without clearly counteracting the progression of the disease. Idalopirdine is an antagonist of the serotonin 6 (5-HT6) receptor, which is expressed in areas of the CNS involved with memory. Given that there is evidence suggesting that the blockade of 5-HT6 receptors induces acetylcholine release, it became reasonable to consider that 5-HT6 antagonism could also be a promising approach for restoring acetylcholine levels in a deteriorated cholinergic system. Areas covered: This review discusses the history leading to the discovery of Idalopirdine, its pharmacokinetics and pharmacodynamics profile and safety issues, together with an overview of clinical trials carried out so far. A literature search was performed with PubMed using the keywords Idalopirdine, AD and 5-HT6 antagonists. The article is also based on information derived from the ClinicalTrials.gov site for clinical trials with Idalopirdine. Expert opinion: Idalopirdine is safe and well tolerated. It could be used as add-on therapy to potentiate the effect of available AChEIs in AD. Nevertheless, results from ongoing Phase III trials are needed to verify whether this drug has a significant clinical effect on cognition in association with AChEIs.
Efficacy and safety of Idalopirdine for Alzheimer's disease: a systematic review and meta-analysis
Int Psychogeriatr 2019 Nov;31(11):1627-1633.PMID:30560763DOI:10.1017/S1041610218002156.
Objective: The efficacy and tolerability of Idalopirdine, a selective 5-hydroxytryptamine6 receptor antagonist, in patients with Alzheimer's disease (AD) is uncertain. A systematic review and meta-analysis of randomized controlled trials (RCTs) testing Idalopirdine for patients with AD was performed. Methods: We included RCTs of Idalopirdine for patients with AD and used Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog) scores as a primary measure. Results: Four RCTs with 2,803 patients with AD were included. There was no significant difference in ADAS-cog between the Idalopirdine and placebo groups [mean difference (MD) = -0.41, P = 0.32, I2 = 62%]. However, significant heterogeneity remained. Sensitivity analysis revealed that Idalopirdine was more effective than placebo for ADAS-cog in the high dose and moderate AD subgroups (high dose subgroup: MD = -2.15, P = 0.005, moderate AD subgroup: MD = -2.15, P = 0.005). Moreover, meta-regression analysis showed that Idalopirdine effect size for ADAS-cog was associated with mean dose (coefficient, -0.0289), ADAS-cog at baseline (coefficient, -0.9519), and proportion of male participants (coefficient, 0.2214). For safety outcomes, Idalopirdine was associated with a higher incidence of at least one adverse event and increased γ-glutamyltransferase, alanine aminotransferase, aspartate aminotransferase, and vomiting than placebo. There were no significant differences in other secondary outcomes between both treatments. Conclusions: Idalopirdine is not effective for AD patients and is associated with a risk of elevated liver enzymes and vomiting. Although Idalopirdine might be more effective at high doses and in moderate AD subgroups, the effect size is small and may be limited.
Idalopirdine, a selective 5-HT6 receptor antagonist, reduces food intake and body weight in a model of excessive eating
Metab Brain Dis 2018 Jun;33(3):733-740.PMID:29297106DOI:10.1007/s11011-017-0175-1.
Obesity, from early childhood onwards, is a common societal problem. The overconsumption of sweet, salty and high-fat products are the main factors that cause excessive weight gain. It is therefore necessary to search for new drugs that affect satiety centers and reduce the sense of hunger and caloric intake. It has been suggested that the blockade of 5-HT6 receptors may reduce food intake, and since Idalopirdine is a clinically tested, selective 5HT6 receptor antagonist, it was chosen to be examined in animal models of obesity. The activity of Idalopirdine was measured in the rat model of excessive eating. Animals were on a high caloric diet that consisted of milk chocolate with nuts, cheese, salted peanuts and condensed milk. During a four-week experiment, the rats had constant access to standard feed and water ad libitum. Idalopirdine was administered intraperitoneally at a dose 5 mg/kg b.w./day. To establish whether Idalopirdine would effectively suppress the rebound hyperphagia that accompanies refeeding, it was administered after a 20 h food deprivation period. Pica behavior was evaluated after the administration of Idalopirdine to confirm that the suppression of food intake was not caused by visceral illness. The effect of the four-week treatment with Idalopirdine on the amount of peritoneal adipose tissue, and on lipid and carbohydrate profiles in rats was also examined. The statistical significance was calculated using the one-way ANOVA post-hoc Tukey Multiple Comparison Test or the two-way ANOVA post-hoc Bonferroni Multiple Comparison Test. Idalopirdine significantly reduced caloric intake and prevented the development of obesity in tested animals. Rats, that received Idalopirdine, had a smaller amount of adipose tissue in the peritoneum as well as lower glucose, triglyceride and cholesterol levels in comparison to the control group. Moreover, an anorectic action was not caused by abnormalities of the gastrointestinal tract, such as nausea. The obtained results indicate that Idalopirdine reduces caloric intake and could be considered for further tests as a potential treatment of obesity.
Idalopirdine - a small molecule antagonist of 5-HT6 with therapeutic potential against obesity
Metab Brain Dis 2015 Dec;30(6):1487-94.PMID:26419385DOI:10.1007/s11011-015-9736-3.
5HT6 receptor antagonists offer the potential for safe and effective drugs against obesity, because they can reduce weight without causing serious side effects in the cardiovascular system. Also, their anorexic effect is associated with reduced food intake via an enhancement of satiety. In the present study we investigated the anorexic effect of Idalopirdine (LuAE58054) in a model of obesity induced by high-fat diet. To induce obesity in rats, the animals were treated with feed with a fat content of 40 %. Body weight was controlled and the amount of food and water consumed was determined. The influence of the test compound on the lipid profile and glucose level was measured, as well as locomotor activity in home cages on the 20th day of the treatment. LuAE58054, at 5 mg kg(-1)/day i.p., was significantly anorectic in this model of obesity. Animals treated with LuAE58054 weighed 8 and 9.2 % less than the control obese animals on the 12th and 21st days, respectively. It significantly reduced food intake and the amount of peritoneal fat in animals, and reduced the level of triglycerides in plasma. LuAE58054 did not have a statistically significant effect on the spontaneous activity of diet-induced obese rats. The present study clearly demonstrates the effectiveness of LuAE58054 in reducing body weight. This compound is in phase III of clinical trials for the treatment of cognitive deficits associated with Alzheimer's disease and schizophrenia. It is a 5HT6 receptor antagonist and is, therefore, free of those unacceptable side effects that preclude chronic use of anti-obesity drugs with other mechanisms of action. The search for an effective and safe anti-obesity drug is essential for an increasingly obese population; therefore, the anorectic action of LuAE58054 is important and there is a need for more research in this direction.
Co-treatment with rivastigmine and Idalopirdine reduces the propensity for falls in a rat model of falls in Parkinson's disease
Psychopharmacology (Berl) 2019 Jun;236(6):1701-1715.PMID:30607479DOI:10.1007/s00213-018-5150-y.
Rationale: Falls in patients with Parkinson's disease (PD) are associated with cognitive, specifically attentional impairments and with losses in cholinergic projection systems. We previously established an animal model of the combined basal forebrain cholinergic-striatal dopaminergic losses of PD fallers (Dual Lesioned, DL, rats) and demonstrated that treating DL rats with an acetylcholinesterase inhibitor (AChEI), donepezil, together with a 5HT6 receptor antagonist, Idalopirdine, reduced fall frequency and improved associated aspects of the performance of DL rats traversing rotating rods. Objectives: Here, we employed a longer and more taxing rotating beam apparatus to determine the potential therapeutic efficacy of Idalopirdine when combined with the pseudo-irreversible, and thus relatively long-acting, AChE- and butyrylcholinesterase- (BuChE) inhibitor rivastigmine. Results: As before, vehicle-treated DL rats fell more frequently, committed more slips, and exhibited more movement stoppages than intact control rats. Repeated intermittent administration of rivastigmine and Idalopirdine significantly improved the performance of DL rats. Rivastigmine alone also produced strong trends for reducing falls and slips. The combination treatment was more effective than rivastigmine alone in reducing stoppages and stoppage-associated falls. As before, Idalopirdine treatment alone was ineffective. Conclusions: These results extend the prediction that the combined treatment with Idalopirdine and an AChEI improves complex movement control and reduces the propensity for falls in patients with movement disorders. Because of the importance of finding better treatments for gait and balance deficits in PD, the present results may further motivate a clinical exploration of the usefulness of this combination treatment.