5-HT₆ Receptor ( Ki = 0.83 nM )
Lu AE58054 (Idalopirdine): Selective 5-HT₆ receptor antagonist [1]
- Lu AE58054 (Idalopirdine): Selective 5-HT₆ receptor antagonist with high affinity [2]

Idalopirdine (intraperitoneal injection, 5 mg/kg, daily, 28 days) can lower body weight and food intake in rat models of overeating[1].
Idalopirdine (1 or 2 mg/kg, i.v) can improve donepezil's effect on cortical gamma oscillations and dose-dependently raise the gamma power during nPO electrical stimulation[2]. However, it has no effect on the rats' sleep-wake cycles.

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Effects on food intake, body weight, and metabolic parameters in excessive eating model rats:
- Lu AE58054 (Idalopirdine) was administered intraperitoneally at 5 mg/kg body weight per day to male Wistar rats for 28 consecutive days. The rats had free access to standard feed, water, and a high-caloric diet (including milk chocolate with nuts, cheese, salted peanuts, condensed milk). Compared with the vehicle-treated palatable control group, Idalopirdine significantly reduced caloric intake and prevented obesity development. The treated rats had less peritoneal adipose tissue, and lower plasma glucose, triglyceride, and total cholesterol levels. [1]
- After a 20-hour food deprivation period, a single administration of Lu AE58054 (Idalopirdine) effectively suppressed rebound hyperphagia during refeeding. [1]
- Pica behavior evaluation showed that Lu AE58054 (Idalopirdine) did not increase kaolin intake, indicating that its anorectic effect was not caused by visceral illness such as nausea. [1]
- Effects on cortical gamma oscillations and sleep-wake architecture in rats:
- Anesthetized rats: Intravenous administration of Lu AE58054 (Idalopirdine) at 2 mg/kg increased gamma power in the medial prefrontal cortex (mPFC) during electrical stimulation of the brainstem nucleus pontis oralis (nPO). Pretreatment with Idalopirdine (2 mg/kg i.v.) potentiated and prolonged the gamma power-increasing effect of donepezil (0.3 and 1 mg/kg i.v.). [2]
- Awake, freely moving rats: Oral administration of Lu AE58054 (Idalopirdine) at 10 mg/kg augmented the gamma power-increasing effect of donepezil (1 mg/kg s.c.) in the frontal cortex. Donepezil (1 and 3 mg/kg s.c.) dose-dependently delayed sleep onset and decreased time spent in REM and non-REM sleep, but Idalopirdine (10 mg/kg p.o.) alone did not affect sleep-wake architecture nor modify the sleep-related effects of donepezil. [2]

Male Wistar rats
5 mg/kg
intraperitoneal injection, daily, 28 days

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Chronic administration in excessive eating model rats:
1. Animal preparation: Use male Wistar rats, randomly divided into groups (n=6 per group). The control groups received 5% 2-hydroxypropyl-beta-cyclodextrin, and the experimental group received Lu AE58054 (Idalopirdine).
2. Diet and housing: All rats had constant access to standard feed and water ad libitum. The palatable diet group (including vehicle and Idalopirdine-treated subgroups) had access to a high-caloric diet (milk chocolate with nuts, cheese, salted peanuts, condensed milk) throughout the 4-week experiment.
3. Drug administration: Lu AE58054 (Idalopirdine) was dissolved in 5% 2-hydroxypropyl-beta-cyclodextrin and administered intraperitoneally at 5 mg/kg body weight once daily for 28 consecutive days.
4. Measurements: Record body weight, food intake (standard and high-caloric), and water intake regularly. After 4 weeks, anesthetize rats with thiopental (70 mg/kg b.w.) after heparin (1000 IU/rat) administration, collect blood to measure plasma glucose, triglyceride, and total cholesterol levels, and dissect to weigh peritoneal adipose tissue.
5. Additional tests: For rebound hyperphagia assessment, administer Idalopirdine once after a 20-hour food deprivation and record food intake. For pica behavior evaluation, measure kaolin intake, food intake, water intake, and body weight after a single administration of Idalopirdine. [1]
- Electrophysiological and sleep-wake architecture studies in rats:
1. Anesthetized rat experiment: Use anesthetized rats, implant electrodes in the medial prefrontal cortex (mPFC) to record neuronal network oscillations. Electrically stimulate the brainstem nucleus pontis oralis (nPO) and measure gamma power in the mPFC. Administer Lu AE58054 (Idalopirdine) (2 mg/kg i.v.) alone or as pretreatment before donepezil (0.3 and 1 mg/kg i.v.), and record gamma power changes.
2. Awake rat experiment: Use freely moving rats with implanted EEG electrodes. Administer Lu AE58054 (Idalopirdine) (10 mg/kg p.o.) as pretreatment before donepezil (1 and 3 mg/kg s.c.), record frontal cortical gamma power via EEG. For sleep-wake architecture analysis, use telemetric polysomnography to monitor sleep stages (REM and non-REM) and wakefulness after drug administration, and analyze sleep onset time and duration in each stage. [2]

Safety was assessed in an overeating model rat: Lu AE58054 (edalopyridine) (5 mg/kg, intraperitoneally daily for 28 days) did not induce pica (no increase in kaolin intake), indicating no visceral disease or nausea-related toxicity. No other significant adverse effects were reported in the experiment. [1]

[1]. 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.

[2]. The 5-HT6 receptor antagonist idalopirdine potentiates the effects of donepezil on gamma oscillations in the frontal cortex of anesthetized and awake rats without affecting sleep-wake architecture. Neuropharmacology. 2017 Feb;113(Pt A):45-59.

SGS518 is a novel 5-HT6 receptor antagonist currently being developed for the treatment of cognitive impairment (CIAS) associated with schizophrenia. Idalopyridine has been used in clinical trials for the treatment of cognitive impairment, schizophrenia, and Alzheimer's disease. Drug Indications It has been investigated for the treatment of neurological disorders, schizophrenia, and schizoaffective disorder. Mechanism of Action SGS518 is a selective 5-HT6 receptor antagonist whose mechanism of action is believed to enhance the transmission of chemicals in the brain. Therapeutic Potential: Lu AE58054 (Idalopyridine) is a clinically tested selective 5-HT₆ receptor antagonist. Its ability to reduce calorie intake, decrease weight, and improve metabolic parameters (lowering blood glucose, triglycerides, and cholesterol) suggests its potential for treating obesity. [1] - Adjunctive therapy for Alzheimer's disease: Lu AE58054 (edalopyridine) is being developed as an adjunctive therapy to acetylcholinesterase inhibitors (AChEIs) for the treatment of mild to moderate Alzheimer's disease. It enhances the effect of donepezil (an AChEI) on cortical gamma oscillations (a pharmacodynamic biomarker related to cognition) without affecting sleep-wake rhythms, which may help improve cognitive function in patients with Alzheimer's disease. [2] - Mechanism-related insights: Blocking 5-HT₆ receptors is considered a potential mechanism of the anorexia effect of Lu AE58054 (edalopyridine) because 5-HT₆ receptor antagonists are known to target satiety centers, reduce hunger, and decrease calorie intake. [1]

C₂₀H₁₉F₅N₂O

398.37

398.141

C, 60.30; H, 4.81; F, 23.84; N, 7.03; O, 4.02

467459-31-0

Idalopirdine Hydrochloride; 467458-02-2

21071390

Solid powder

1.3±0.1 g/cm3

500.9±50.0 °C at 760 mmHg

256.7±30.1 °C

0.0±1.3 mmHg at 25°C

1.553

4.38

2

7

9

28

482

0

FC1=CC(NC=C2CCNCC3=CC(OCC(F)(C(F)F)F)=CC=C3)=C2C=C1

YBAWYTYNMZWMMJ-UHFFFAOYSA-N

InChI=1S/C20H19F5N2O/c21-15-4-5-17-14(11-27-18(17)9-15)6-7-26-10-13-2-1-3-16(8-13)28-12-20(24,25)19(22)23/h1-5,8-9,11,19,26-27H,6-7,10,12H2

2-(6-fluoro-1H-indol-3-yl)-N-[[3-(2,2,3,3-tetrafluoropropoxy)phenyl]methyl]ethanamine

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)

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

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Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*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.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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