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| Targets |
Piromelatine targets multiple receptors and ion channels. It acts as an agonist at melatonin MT1/MT2 receptors and serotonin 5-HT1A/5-HT1D receptors, and as an antagonist at 5-HT2B receptors. The compound also inhibits P2X3, TRPV1, and Nav1.7 channels. This multimodal mechanism contributes to its wide range of potential therapeutic effects.
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| ln Vitro |
In vitro, Piromelatine acts as an agonist at MT1/MT2 and 5-HT1A/5-HT1D receptors, an antagonist at 5-HT2B receptors, and an inhibitor of P2X3, TRPV1, and Nav1.7 channels. Its activity is typically assessed in receptor binding assays measuring affinity for these targets and in functional assays measuring receptor-mediated signaling or ion channel inhibition.
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| ln Vivo |
Treatment with Piromelatine (20 mg/kg, intraperitoneally, daily) reverses sleep restriction-induced insulin resistance [1]. Piromelatine (5-50 mg/kg, intraperitoneally, daily) significantly decreases plasma glucose [2]. Piromelatine (100 mg/kg) decreases heat hyperalgesia and mechanical allodynia in PSL (partial sciatic nerve ligation) mice [3].
In vivo, Piromelatine possesses sleep-promoting, analgesic, anti-neurodegenerative, anxiolytic, and antidepressant potentials. It is a multimodal sleep-regulating agent under development by Neurim Pharmaceuticals. The compound's diverse pharmacological profile supports its potential for treating multiple neurological and psychiatric conditions. |
| Enzyme Assay |
In cell-free receptor binding assays, Piromelatine's activity is evaluated by measuring its affinity for MT1/MT2, 5-HT1A/5-HT1D, and 5-HT2B receptors. Membrane preparations from cells expressing these receptors are incubated with radiolabeled ligands and varying concentrations of Piromelatine. The displacement of the radioligands is measured, and the Ki values are calculated from competition curves.
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| Cell Assay |
In vitro cell-based experiments with Piromelatine typically involve cell lines expressing the target receptors or ion channels. Cells are treated with the compound, and receptor activation or ion channel inhibition is assessed by measuring downstream signaling events (e.g., cAMP accumulation, calcium mobilization) or by electrophysiological techniques. The EC50 or IC50 for each target is determined from concentration-response curves.
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| Animal Protocol |
Animal/Disease Models: 24 male SD (SD (Sprague-Dawley)) rats (3 months old, weight 250-300g) [1].
Doses: 20 mg/kg. Route of Administration: intraperitoneal (ip) injection, every evening at 8:00 pm Experimental Results: resulted in a significant decrease in plasma glucose levels (6.670.35 mmol/L, 6.770.34 mmol/L vs. 8.27 0.38 mmol/L), and both plasma glucose levels The Dramatically diminished group was even close to the normal control group (6.07±0.35 mmol/L). This resulted in a decrease in triglyceride and total cholesterol levels (51.8% and 43.0%, respectively) and an increase in HDL-C levels (32.4% increase). Animal/Disease Models: 5 groups of 12weeks old rats (10/group) [2]. Doses: 5-50 mg/kg. Route of Administration: intraperitoneal (ip) injection at 18:00 every day. Experimental Results: Plasma glucose was Dramatically diminished by 27.3%, 34.5% and 61.5% respectively. Animal/Disease Models: Male C57BL/6 J mice, weighing 22-26 grams (10 weeks old; PSL mice) [3]. Doses: 25, 50 or 100 mg/kg. Route of Administration: IP injection was performed 1 hour before assessment of thermal hype In vivo animal experiments with Piromelatine have been conducted in various models to evaluate its sleep-promoting, analgesic, anxiolytic, and antidepressant effects. In typical protocols, rodents are administered the compound, and sleep-wake cycles are monitored by EEG/EMG. Pain responses are measured in models of nociception. Behavioral tests such as the elevated plus maze and forced swim test are used to assess anxiolytic and antidepressant effects. |
| ADME/Pharmacokinetics |
No detailed pharmacokinetic data is publicly available for Piromelatine. As a multimodal agent, its absorption, distribution, metabolism, and excretion (ADME) properties would be expected to support its central nervous system activity. Its half-life and bioavailability have not been extensively characterized.
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| Toxicity/Toxicokinetics |
No specific toxicity data is publicly available for Piromelatine. In preclinical studies, the compound has shown a range of therapeutic potentials without reported significant toxicity. The compound is for research use only and is not intended for human therapeutic applications outside of approved clinical trials.
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| References |
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| Additional Infomation |
Piromeratine has been used in trials investigating the treatment of Alzheimer's disease.
Piromelatine has a CAS number of 946846-83-9. It is also known as Neu-P11 and N-[2-(5-Methoxy-1H-indol-3-yl)ethyl]-4-oxo-4H-pyran-2-carboxamide. The compound is a multimodal agonist at melatonin MT1/MT2 and serotonin 5-HT1A/5-HT1D receptors, an antagonist at 5-HT2B, and an inhibitor of P2X3, TRPV1, and Nav1.7 channels. It possesses sleep-promoting, analgesic, anti-neurodegenerative, anxiolytic, and antidepressant potentials. |
| Molecular Formula |
C17H16N2O4
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|---|---|
| Molecular Weight |
312.325
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| Exact Mass |
312.111
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| CAS # |
946846-83-9
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| PubChem CID |
24815904
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| Appearance |
Light yellow to yellow solid powder
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| LogP |
2.493
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
23
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| Complexity |
529
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
PNTNBIHOAPJYDB-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C17H16N2O4/c1-22-13-2-3-15-14(9-13)11(10-19-15)4-6-18-17(21)16-8-12(20)5-7-23-16/h2-3,5,7-10,19H,4,6H2,1H3,(H,18,21)
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| Chemical Name |
N-[2-(5-methoxy-1H-indol-3-yl)ethyl]-4-oxopyran-2-carboxamide
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| Synonyms |
NEU-P-11; NEU-P 11; NEU-P11
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: This product requires protection from light (avoid light exposure) during transportation and storage. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ~250 mg/mL (~800.46 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (6.66 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 20.8 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. Solubility in Formulation 2: ≥ 2.08 mg/mL (6.66 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in 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 20.8 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.2017 mL | 16.0087 mL | 32.0174 mL | |
| 5 mM | 0.6403 mL | 3.2017 mL | 6.4035 mL | |
| 10 mM | 0.3202 mL | 1.6009 mL | 3.2017 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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