PIROMELATINE

Investigational

Details

Stereochemistry	ACHIRAL
Molecular Formula	C17H16N2O4
Molecular Weight	312.3199
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

COC1=CC2=C(NC=C2CCNC(=O)C3=CC(=O)C=CO3)C=C1

InChI

InChIKey=PNTNBIHOAPJYDB-UHFFFAOYSA-N

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)

HIDE SMILES / InChI

Molecular Formula	C17H16N2O4
Molecular Weight	312.3199
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: https://adisinsight.springer.com/drugs/800032086 | https://alzheimersnewstoday.com/piromelatine/ | https://www.alzforum.org/therapeutics/piromelatine

Piromelatine is an investigational therapy being developed by Neurim Pharmaceuticals to manage sleeping difficulties. The compound is now being studied for its potential to improve cognitive function and slow the progression of Alzheimer’s disease by promoting better sleep. It acts primarily as an agonist of MT1/MT2/MT3 melatonin receptors and serotonin 5-HT1A and 5-HT1D receptors, but reportedly also is a low-affinity antagonist of 5-HT2B, P2X3, and TRPV1 receptors. Piromelatine may benefit control of circadian rhythm, metabolism, cognition and mood. Preclinical studies have reported cognitive improvement in rats that received hippocampal Aβ42 injections to simulate Alzheimer’s disease. There are also reports on painkilling and hypnotic effects in a mouse model of neuropathic pain, as well as blood pressure lowering in rats. Piromelatine is in phase II clinical trial for the treatment of Alzheimer's disease, Insomnia, Ocular hypertension and Open-angle glaucoma.

Originator

Approval Year

PubMed

Title	Date	PubMed
Insomnia in Elderly Patients: Recommendations for Pharmacological Management.	2018-09	30058034
Melatonin Receptor Agonist Piromelatine Ameliorates Impaired Glucose Metabolism in Chronically Stressed Rats Fed a High-Fat Diet.	2018-01	29025979
Circadian Rhythm and Melatonin in the Treatment of Depression.	2018	30073921
Neu-P11, a novel MT1/MT2 agonist, reverses diabetes by suppressing the hypothalamic-pituitary-adrenal axis in rats.	2017-10-05	28687198
Inflammaging, Metabolic Syndrome and Melatonin: A Call for Treatment Studies.	2017	27165273
Anticonvulsant activity of melatonin, but not melatonin receptor agonists Neu-P11 and Neu-P67, in mice.	2016-07-01	27016427
Piromelatine ameliorates memory deficits associated with chronic mild stress-induced anhedonia in rats.	2016-06	27007604
Role of Neu-p11/luzindole in the regulation of insulin signaling pathways and insulin resistance.	2016-05	27025603
Melatonin, but not melatonin receptor agonists Neu-P11 and Neu-P67, attenuates TNBS-induced colitis in mice.	2016-05	26899972
Melatonin and Synthetic Melatoninergic Agonists in Psychiatric and Age-associated Disorders: Successful and Unsuccessful Approaches.	2016	25248806
Neuroprotective mechanism of the novel melatonin derivative Neu-P11 in brain ischemia related models.	2015-12	26188145
Current Phase II investigational therapies for insomnia.	2015-03	25423562
Exploration on mechanism of a new type of melatonin receptor agonist Neu-p11 in hypoxia-reoxygenation injury of myocardial cells.	2014-11	24840226
Piromelatine exerts antinociceptive effect via melatonin, opioid, and 5HT1A receptors and hypnotic effect via melatonin receptors in a mouse model of neuropathic pain.	2014-10	24700387
Piromelatine, a novel melatonin receptor agonist, stabilizes metabolic profiles and ameliorates insulin resistance in chronic sleep restricted rats.	2014-03-15	24486392
Antinociceptive effects of novel melatonin receptor agonists in mouse models of abdominal pain.	2014-02-07	24574803
Blood pressure reducing effects of piromelatine and melatonin in spontaneously hypertensive rats.	2013-09	24089222
Neu-p11 reduces clock/apelin expression in insulin-resistant mouse adipocyte model.	2013-09	23963596
Piromelatine decreases triglyceride accumulation in insulin resistant 3T3-L1 adipocytes: role of ATGL and HSL.	2013-08	23707538
A novel melatonin agonist Neu-P11 facilitates memory performance and improves cognitive impairment in a rat model of Alzheimer' disease.	2013-06	23651610
Determination of the novel melatonin agonist Neu-P11 in plasma samples by liquid chromatography-tandem mass spectrometry.	2013-02-23	23245235
Elucidation of Neu-P11 metabolism in urine of volunteers by liquid chromatography-tandem mass spectrometry.	2013-02-22	23336948
Cardiovascular effects of melatonin receptor agonists.	2012-11	22916799
Antidepressant- and anxiolytic effects of the novel melatonin agonist Neu-P11 in rodent models.	2010-07	20581849
Investigational melatonin receptor agonists.	2010-06	20408738
NEU-P11, a novel melatonin agonist, inhibits weight gain and improves insulin sensitivity in high-fat/high-sucrose-fed rats.	2009-04	19429466

Patents

Substance Class	Chemical Created by `admin` on `Mon Mar 31 20:48:41 GMT 2025` Edited by `admin` on `Mon Mar 31 20:48:41 GMT 2025`
Record UNII	S3UN2146K9
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

PIROMELATINE

Official Name

English

piromelatine [INN]

Preferred Name

English

4H-PYRAN-2-CARBOXAMIDE, N-(2-(5-METHOXY-1H-INDOL-3-YL)ETHYL)-4-OXO-

Systematic Name

English

NEU-P-11

Code

English

N-(2-(5-METHOXY-1H-INDOL-3-YL)ETHYL)-4-OXO-4H-PYRAN-2-CARBOXAMIDE

Systematic Name

English

Piromelatine [WHO-DD]

Common Name

English

NEU-P11

Code

English

Code System Code Type Description

SMS_ID

300000034334