| Identification | Back Directory | [Name]
Piromelatine | [CAS]
946846-83-9 | [Synonyms]
NEU-P11
NEU-P-11
NEU-P 11
Piromelatine
Piromelatine (Neu-P11)
Piromelatine 946846-83-9
N-[2-(5-methoxy-1H-indol-3-yl)ethyl]-4-oxopyran-2-carboxamide
4H-Pyran-2-carboxamide, N-[2-(5-methoxy-1H-indol-3-yl)ethyl]-4-oxo- | [Molecular Formula]
C17H16N2O4 | [MDL Number]
MFCD30146157 | [MOL File]
946846-83-9.mol | [Molecular Weight]
312.32 |
| Hazard Information | Back Directory | [Description]
Piromelatine is a novel investigational agent that has agonist activity at MT1 and MT2 along with agonism at 5-HT1A/1D receptors. A phase II randomized clinical trial (N 1/4 120) in primary insomnia resulted in significant improvement in insomnia symptoms. | [Uses]
Piromelatine (Neu-P11) is a melatonin MT1/MT2 receptor agonist, serotonin 5-HT1A/5-HT1D agonist, and serotonin 5-HT2B antagonist. Piromelatine (Neu-P11) possesses sleep promoting, analgesic, anti-neurodegenerative, anxiolytic and antidepressant potentials. Piromelatine (Neu-P11) also possesses pain-related P2X3, TRPV1, and Nav1.7 channel-inhibition capacities[1][2][3]. | [in vivo]
Piromelatine (20 mg/kg, ip, daily) treatment prevents insulin resistance induced by sleep restriction[1].
Piromelatine (5-50 mg/kg, ip, daily) decreases plasma glucose significantly[2].
Piromelatine (100 mg/kg) decreases thermal hyperalgesia and mechanical allodynia in PSL (partial sciatic nerve ligation) mice[3].
| Animal Model: | Twenty four male Sprague-Dawley rats (3 months old, weighing 250-300 g)[1]. | | Dosage: | 20 mg/kg. | | Administration: | IP, daily at 8:00 p.m. | | Result: | Resulted in significantly decreased plasma glucose levels (6.670.35 mmol/L, 6.770.34 mmol/L vs. 8.27 0.38 mmol/L), and the plasma glucose levels of the two groups were even neared to that of the normal control group (6.07±0.35 mmol/L).
Resulted in a decrease in triglycerides and total cholesterol levels (51.8% and
43.0%, respectively) and an elevation in HDL-C level (increase of 32.4%).
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| Animal Model: | Five groups of 12-wk-old rats (10/group)[2]. | | Dosage: | 5-50 mg/kg. | | Administration: | Intraperitoneal injection in 18:00 every day. | | Result: | Plasma glucose was decreased significantly by 27.3%, 34.5% and 61.5%, respectively. |
| Animal Model: | Male C57BL/6 J mice, weighing 22-26 g (10 weeks old; PSL mice)[3]. | | Dosage: | 25, 50, or 100 mg/kg. | | Administration: | IP 1 h before assessment of thermal hyperalgesia and mechanical allodynia. | | Result: | Remarkably prolonged thermal latency (surgery×treatment interaction, F1,24=15.7, p<0.001; surgery×treatment×hours interaction, F5,120=3.0, p<0.05) and increased mechanical threshold (surgery×treatment interaction, F1,24=18.4, p<0.001; surgery× treatment×hours interaction, F5,120=2.6, p<0.05) for 4 h after administration of piromelatine to PSL mice. |
| [IC 50]
MT1; MT2; 5-HT1A Receptor; 5-HT1D Receptor; 5-HT2B Receptor | [Clinical claims and research]
Piromelatine known as Neu-P11 is a newer melatonin receptor agonist underdevelopmental stage. It acts on MT1, MT2, and also 5-HT1A/5- HT1D receptors. It has demonstrated improvement in the sleep cycle of primary insomnia patients and reducing sleep disturbances in Phase II clinical trial. It was found to have efficacy in maintaining deeper sleep, less arousal, and also preserving REM sleep pattern. In the clinical trial, piromelatine was well tolerated with no adverse effects on psychomotor performance the following day (She et al., 2014). | [References]
[1] Meihua She, et al. Piromelatine, a Novel Melatonin Receptor Agonist, Stabilizes Metabolic Profiles and Ameliorates Insulin Resistance in Chronic Sleep Restricted Rats. Eur J Pharmacol. 2014 Mar 15;727:60-5. DOI:10.1016/j.ejphar.2014.01.037
[2] L Huang, et al. Blood Pressure Reducing Effects of Piromelatine and Melatonin in Spontaneously Hypertensive Rats. Eur Rev Med Pharmacol Sci. 2013 Sep;17(18):2449-56. PMID:24089222
[3] Yuan-Yuan Liu, et al. Piromelatine Exerts Antinociceptive Effect via Melatonin, Opioid, and 5HT1A Receptors and Hypnotic Effect via Melatonin Receptors in a Mouse Model of Neuropathic Pain. Psychopharmacology (Berl). 2014 Oct;231(20):3973-85. DOI:10.1007/s00213-014-3530-5 |
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