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Piromelatine
Identifiers

IUPAC name N-[2-(5-Methoxy-1H-indol-3-yl)ethyl]-4-oxopyran-2-carboxamide
CAS Number	946846-83-9
PubChem CID
Chemical and physical data
Formula	C₁₇H₁₆N₂O₄
Molar mass	312.325 g·mol⁻¹
3D model (JSmol)	Interactive image
SMILES COC1=CC2=C(C=C1)NC=C2CCNC(=O)C3=CC(=O)C=CO3
InChI 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) Key:PNTNBIHOAPJYDB-UHFFFAOYSA-N

Piromelatine (Neu-P11) is a multimodal sleep drug under development by Neurim Pharmaceuticals. It is an agonist at melatonin MT₁/MT₂ and serotonin 5-HT_1A/5-HT_1D receptors. Neurim is conducting a phase II randomized, placebo controlled trial of cognitive and sleep effects in Alzheimer's disease.

Results of a phase II trial on insomnia in 120 adults were announced in 2013, finding piromelatine 20/50 mg improved sleep over 4 weeks vs placebo.^[1] Phase 1A/1B studies in 2011, showed safe dose-dependent improvement in sleep.^[2] Pre-clinical studies showed antinociceptive^[3] antihypertensive^[4] and cognitive benefits^[5] in rat disease models of pain, hypertension, and Alzheimer's disease.

Antidepressant and anti-anxiety effects were also demonstrated in animal models.^[6]

References

^ "Neurim Pharmaceuticals Announces Positive Phase 2 Clinical Trial Results of Piromelatine for the Treatment of Insomnia". Neurim Pharmaceuticals. 18 February 2013.
^ "Neurim Pharmaceuticals Announces Positive Results From Phase I and Ib Clinical Trials With Neu-p11, a Sleep Maintenance Drug". Neurim Pharmaceuticals. 24 July 2011.
^ Liu YY, Yin D, Chen L, Qu WM, Chen CR, Laudon M, et al. (October 2014). "Piromelatine exerts antinociceptive effect via melatonin, opioid, and 5HT1A receptors and hypnotic effect via melatonin receptors in a mouse model of neuropathic pain". Psychopharmacology. 231 (20): 3973–85. doi:10.1007/s00213-014-3530-5. PMID 24700387. S2CID 815868.
^ Huang L, Zhang C, Hou Y, Laudon M, She M, Yang S, et al. (September 2013). "Blood pressure reducing effects of piromelatine and melatonin in spontaneously hypertensive rats". European Review for Medical and Pharmacological Sciences. 17 (18): 2449–56. PMID 24089222.
^ He P, Ouyang X, Zhou S, Yin W, Tang C, Laudon M, Tian S (June 2013). "A novel melatonin agonist Neu-P11 facilitates memory performance and improves cognitive impairment in a rat model of Alzheimer' disease". Hormones and Behavior. 64 (1): 1–7. doi:10.1016/j.yhbeh.2013.04.009. PMID 23651610. S2CID 205806140.
^ Tian SW, Laudon M, Han L, Gao J, Huang FL, Yang YF, Deng HF (July 2010). "Antidepressant- and anxiolytic effects of the novel melatonin agonist Neu-P11 in rodent models". Acta Pharmacologica Sinica. 31 (7): 775–783. doi:10.1038/aps.2010.80. PMC 4007730. PMID 20581849.

v t e Melatonin receptor modulators
MT₁Tooltip Melatonin receptor 1	Agonists: 2-Iodomelatonin 6-Hydroxymelatonin Agomelatine Fabomotizole (afobazole) GR-196,429 Melatonin N-Acetylserotonin (normelatonin) Piromelatine Ramelteon Tasimelteon TIK-301 (LY-156,735) Antagonists: Luzindole
MT₂Tooltip Melatonin receptor 2	Agonists: 2-Iodomelatonin 6-Hydroxymelatonin Agomelatine GR-196,429 Melatonin N-Acetylserotonin (normelatonin) Piromelatine Ramelteon Tasimelteon TIK-301 (LY-156,735) Antagonists: Luzindole
Unsorted	Agonists: 2-Phenylmelatonin 5-Methoxyluzindole 6-Chloromelatonin 6-Fluoromelatonin 6-Methoxymelatonin 6,7-Dichloro-2-methylmelatonin 8-M-PDOT AMMTC GR-135,531 (of MT₃Tooltip melatonin receptor 1C) N-Acetyltryptamine N-Butanoylmelatonin N-Propionylmelatonin S-24268 S-25150 Antagonists: 4-P-ADOT 4-P-PDOT DH-97 N-Acetyltryptamine (of MT₃) Prazosin (of MT₃) S-20928 S-22153 S-24601 S-25567 S-26131
See also: Receptor/signaling modulators Adrenergics Dopaminergics Serotonergics Monoamine metabolism modulators

Serotonin receptor modulators

5-HT₁

5-HT_1A

Agonists: 8-OH-DPAT Adatanserin Amphetamine Antidepressants (e.g., etoperidone, hydroxynefazodone, nefazodone, trazodone, triazoledione, vilazodone, vortioxetine) Atypical antipsychotics (e.g., aripiprazole, asenapine, brexpiprazole, cariprazine, clozapine, lurasidone, quetiapine, ziprasidone) Azapirones (e.g., buspirone, eptapirone, gepirone, perospirone, tandospirone) Bay R 1531 Befiradol BMY-14802 Cannabidiol Dimemebfe Dopamine Ebalzotan Eltoprazine Enciprazine Ergolines (e.g., bromocriptine, cabergoline, dihydroergotamine, ergotamine, lisuride, LSD, methylergometrine (methylergonovine), methysergide, pergolide) F-11,461 F-12826 F-13714 F-14679 F-15063 F-15,599 Flesinoxan Flibanserin Flumexadol Hypidone Lesopitron LY-293284 LY-301317 mCPP MKC-242 Naluzotan NBUMP Osemozotan Oxaflozane Pardoprunox Piclozotan Rauwolscine Repinotan Roxindole RU-24,969 S-14,506 S-14671 S-15535 Sarizotan Serotonin (5-HT) SSR-181507 Sunepitron Tryptamines (e.g., 5-CT, 5-MeO-DMT, 5-MT, bufotenin, DMT, indorenate, N-Me-5-HT, psilocin, psilocybin) TGBA01AD U-92,016-A Urapidil Vilazodone Xaliproden Yohimbine
Antagonists: Atypical antipsychotics (e.g., iloperidone, risperidone, sertindole) AV965 Beta blockers (e.g., alprenolol, carteolol, cyanopindolol, iodocyanopindolol, isamoltane, oxprenolol, penbutolol, pindobind, pindolol, propranolol, tertatolol) BMY-7,378 CSP-2503 Dotarizine Ergolines (e.g., metergoline) FCE-24379 Flopropione GR-46611 Isamoltane Lecozotan Mefway Metitepine (methiothepin) MIN-117 (WF-516) MPPF NAN-190 Robalzotan S-15535 SB-649,915 SDZ 216-525 Spiperone Spiramide Spiroxatrine UH-301 WAY-100135 WAY-100635 Xylamidine
Unknown/unsorted: Acetryptine Carvedilol Ergolines (e.g., ergometrine (ergonovine))

5-HT_1B

Agonists: Anpirtoline CGS-12066A CP-93129 CP-94253 CP-122,288 CP-135807 Eltoprazine Ergolines (e.g., bromocriptine, dihydroergotamine, ergotamine, methylergometrine (methylergonovine), methysergide, pergolide) mCPP RU-24,969 Serotonin (5-HT) Triptans (e.g., avitriptan, donitriptan, eletriptan, sumatriptan, zolmitriptan) TFMPP Tryptamines (e.g., 5-BT, 5-CT, 5-MT, DMT) Vortioxetine
Antagonists: AR-A000002 Beta blockers (e.g., alprenolol, carteolol, isamoltane, oxprenolol, penbutolol, propranolol, tertatolol) Elzasonan Ergolines (e.g., metergoline) GR-127935 Isamoltane LY-393558 Metitepine (methiothepin) SB-216641 SB-224289 SB-236057 Yohimbine
Unknown/unsorted: Ergolines (e.g., cabergoline, ergometrine (ergonovine), lisuride)

5-HT_1D

Agonists: CP-122,288 CP-135807 CP-286601 Ergolines (e.g., bromocriptine, cabergoline, dihydroergotamine, ergotamine, LSD, methysergide) GR-46611 L-694247 L-772405 mCPP PNU-109291 PNU-142633 Serotonin (5-HT) TGBA01AD Triptans (e.g., almotriptan, avitriptan, donitriptan, eletriptan, frovatriptan, naratriptan, rizatriptan, sumatriptan, zolmitriptan) Tryptamines (e.g., 5-BT, 5-CT, 5-Et-DMT, 5-MT, 5-(nonyloxy)tryptamine, DMT)
Antagonists: Alniditan BRL-15,572 Elzasonan Ergolines (e.g., metergoline) GR-127935 Ketanserin LY-310762 LY-367642 LY-393558 LY-456219 LY-456220 Metitepine (methiothepin) Mianserin Ritanserin Yohimbine Ziprasidone
Unknown/unsorted: Acetryptine Ergolines (e.g., lisuride, lysergol, pergolide)

5-HT_1E

Agonists: BRL-54443 Ergolines (e.g., methysergide) Serotonin (5-HT) Triptans (e.g., eletriptan) Tryptamines (e.g., tryptamine)
Antagonists: Metitepine (methiothepin)
Unknown/unsorted: Ergolines (e.g., ergometrine (ergonovine), lysergol, methylergometrine (methylergonovine)

5-HT_1F

Agonists: BRL-54443 CP-122,288 Ergolines (e.g., bromocriptine, lysergol, methylergometrine (methylergonovine) methysergide) Lasmiditan LY-334370 Serotonin (5-HT) Triptans (e.g., eletriptan, naratriptan, sumatriptan) Tryptamines (e.g., 5-MT)
Antagonists: Metitepine (methiothepin) Mianserin

5-HT₂

5-HT_2A

Agonists: 25H/NB series (e.g., 25I-NBF, 25I-NBMD, 25I-NBOH, 25I-NBOMe, 25B-NBOMe, 25C-NBOMe, 25TFM-NBOMe, 2CBCB-NBOMe, 25CN-NBOH, 2CBFly-NBOMe) 2Cs (e.g., 2C-B, 2C-E, 2C-I, 2C-T-2, 2C-T-7, 2C-T-21) 2C-B-FLY 2CB-Ind 5-Methoxytryptamines (5-MeO-DET, 5-MeO-DiPT, 5-MeO-DMT, 5-MeO-DPT, 5-MT) α-Alkyltryptamines (e.g., 5-Cl-αMT, 5-Fl-αMT, 5-MeO-αET, 5-MeO-αMT, α-Me-5-HT, αET, αMT) AL-34662 AL-37350A Bromo-DragonFLY Dimemebfe DMBMPP DOx (e.g., DOB, DOC, DOI, DOM) Efavirenz Ergolines (e.g., 1P-LSD, ALD-52, bromocriptine, cabergoline, ergine (LSA), ergometrine (ergonovine), ergotamine, lisuride, LA-SS-Az, LSB, LSD, LSD-Pip, LSH, LSP, methylergometrine (methylergonovine), pergolide) Flumexadol IHCH-7113 Jimscaline Lorcaserin MDxx (e.g., MDA (tenamfetamine), MDMA (midomafetamine), MDOH, MMDA) O-4310 Oxaflozane PHA-57378 PNU-22394 PNU-181731 RH-34 SCHEMBL5334361 Phenethylamines (e.g., lophophine, mescaline) Piperazines (e.g., BZP, quipazine, TFMPP) Serotonin (5-HT) TCB-2 TFMFly Tryptamines (e.g., 5-BT, 5-CT, bufotenin, DET, DiPT, DMT, DPT, psilocin, psilocybin, tryptamine)
Antagonists: 5-I-R91150 5-MeO-NBpBrT AC-90179 Adatanserin Altanserin Antihistamines (e.g., cyproheptadine, hydroxyzine, ketotifen, perlapine) AMDA Atypical antipsychotics (e.g., amperozide, aripiprazole, asenapine, blonanserin, brexpiprazole, carpipramine, clocapramine, clorotepine, clozapine, fluperlapine, gevotroline, iloperidone, lurasidone, melperone, mosapramine, ocaperidone, olanzapine, paliperidone, quetiapine, risperidone, sertindole, zicronapine, ziprasidone, zotepine) Chlorprothixene Cinanserin CSP-2503 Deramciclane Dotarizine Eplivanserin Ergolines (e.g., amesergide, LY-53857, LY-215,840, mesulergine, metergoline, methysergide, sergolexole) Fananserin Flibanserin Glemanserin Irindalone Ketanserin KML-010 Landipirdine LY-393558 mCPP Medifoxamine Metitepine (methiothepin) MIN-117 (WF-516) Naftidrofuryl Nantenine Nelotanserin Opiranserin (VVZ-149) Pelanserin Phenoxybenzamine Pimavanserin Pirenperone Pizotifen Pruvanserin Rauwolscine Ritanserin Roluperidone S-14671 Sarpogrelate Serotonin antagonists and reuptake inhibitors (e.g., etoperidone, hydroxynefazodone, lubazodone, mepiprazole, nefazodone, triazoledione, trazodone) SR-46349B TGBA01AD Teniloxazine Temanogrel Tetracyclic antidepressants (e.g., amoxapine, aptazapine, esmirtazapine, maprotiline, mianserin, mirtazapine) Tricyclic antidepressants (e.g., amitriptyline) Typical antipsychotics (e.g., chlorpromazine, fluphenazine, haloperidol, loxapine, perphenazine, pimozide, pipamperone, prochlorperazine, setoperone, spiperone, spiramide, thioridazine, thiothixene, trifluoperazine) Volinanserin Xylamidine Yohimbine
Unknown/unsorted: Ergolines (e.g., dihydroergotamine, nicergoline)

5-HT_2B

Agonists: 4-Methylaminorex Aminorex Amphetamines (e.g., chlorphentermine, cloforex, dexfenfluramine, fenfluramine, levofenfluramine, norfenfluramine) BW-723C86 DOx (e.g., DOB, DOC, DOI, DOM) Ergolines (e.g., cabergoline, dihydroergocryptine, dihydroergotamine, ergotamine, methylergometrine (methylergonovine), methysergide, pergolide) Lorcaserin MDxx (e.g., MDA (tenamfetamine), MDMA (midomafetamine), MDOH, MMDA) Piperazines (e.g., TFMPP) PNU-22394 Ro60-0175 Serotonin (5-HT) Tryptamines (e.g., 5-BT, 5-CT, 5-MT, α-Me-5-HT, bufotenin, DET, DiPT, DMT, DPT, psilocin, psilocybin, tryptamine)
Antagonists: Agomelatine Atypical antipsychotics (e.g., amisulpride, aripiprazole, asenapine, brexpiprazole, cariprazine, clozapine, N-desalkylquetiapine (norquetiapine), N-desmethylclozapine (norclozapine), olanzapine, pipamperone, quetiapine, risperidone, ziprasidone) Cyproheptadine EGIS-7625 Ergolines (e.g., amesergide, bromocriptine, lisuride, LY-53857, LY-272015, mesulergine) Ketanserin LY-393558 mCPP Metadoxine Metitepine (methiothepin) Pirenperone Pizotifen Propranolol PRX-08066 Rauwolscine Ritanserin RS-127445 Sarpogrelate SB-200646 SB-204741 SB-206553 SB-215505 SB-221284 SB-228357 SDZ SER-082 Tegaserod Tetracyclic antidepressants (e.g., amoxapine, mianserin, mirtazapine) Trazodone Typical antipsychotics (e.g., chlorpromazine) TIK-301 Yohimbine
Unknown/unsorted: Ergolines (e.g., ergometrine (ergonovine))

5-HT_2C

Agonists: 2Cs (e.g., 2C-B, 2C-E, 2C-I, 2C-T-2, 2C-T-7, 2C-T-21) 5-Methoxytryptamines (5-MeO-DET, 5-MeO-DiPT, 5-MeO-DMT, 5-MeO-DPT, 5-MT) α-Alkyltryptamines (e.g., 5-Cl-αMT, 5-Fl-αMT, 5-MeO-αET, 5-MeO-αMT, α-Me-5-HT, αET, αMT) A-372159 AL-38022A Alstonine CP-809101 Dimemebfe DOx (e.g., DOB, DOC, DOI, DOM) Ergolines (e.g., ALD-52, cabergoline, dihydroergotamine, ergine (LSA), ergotamine, lisuride, LA-SS-Az, LSB, LSD, LSD-Pip, LSH, LSP, pergolide) Flumexadol Lorcaserin MDxx (e.g., MDA (tenamfetamine), MDMA (midomafetamine), MDOH, MMDA) MK-212 ORG-12962 ORG-37684 Oxaflozane PHA-57378 Phenethylamines (e.g., lophophine, mescaline) Piperazines (e.g., aripiprazole, BZP, mCPP, quipazine, TFMPP) PNU-22394 PNU-181731 Ro60-0175 Ro60-0213 Serotonin (5-HT) Tryptamines (e.g., 5-BT, 5-CT, bufotenin, DET, DiPT, DMT, DPT, psilocin, psilocybin, tryptamine) Vabicaserin WAY-629 WAY-161503 YM-348
Antagonists: Adatanserin Agomelatine Atypical antipsychotics (e.g., asenapine, clorotepine, clozapine, fluperlapine, iloperidone, melperone, olanzapine, paliperidone, quetiapine, risperidone, sertindole, ziprasidone, zotepine) Captodiame CEPC Cinanserin Cyproheptadine Deramciclane Desmetramadol Dotarizine Eltoprazine Ergolines (e.g., amesergide, bromocriptine, LY-53857, LY-215,840, mesulergine, metergoline, methysergide, sergolexole) Etoperidone Fluoxetine FR-260010 Irindalone Ketanserin Ketotifen Latrepirdine (dimebolin) Medifoxamine Metitepine (methiothepin) Nefazodone Pirenperone Pizotifen Propranolol Ritanserin RS-102221 S-14671 SB-200646 SB-206553 SB-221284 SB-228357 SB-242084 SB-243213 SDZ SER-082 Tedatioxetine Tetracyclic antidepressants (e.g., amoxapine, aptazapine, esmirtazapine, maprotiline, mianserin, mirtazapine) TIK-301 Tramadol Trazodone Tricyclic antidepressants (e.g., amitriptyline, nortriptyline) Typical antipsychotics (e.g., chlorpromazine, loxapine, pimozide, pipamperone, thioridazine) Xylamidine
Unknown/unsorted: Efavirenz Ergolines (e.g., ergometrine (ergonovine), methylergometrine (methylergonovine))

5-HT₃_–7

5-HT₃

Agonists: Alcohols (e.g., butanol, ethanol (alcohol), trichloroethanol) m-CPBG Phenylbiguanide Piperazines (e.g., BZP, mCPP, quipazine) RS-56812 Serotonin (5-HT) SR-57227 SR-57227A Tryptamines (e.g., 2-Me-5-HT, 5-CT, bufotenidine (5-HTQ)) Volatiles/gases (e.g., halothane, isoflurane, toluene, trichloroethane) YM-31636
Antagonists: Alosetron Anpirtoline Arazasetron AS-8112 Atypical antipsychotics (e.g., clozapine, olanzapine, quetiapine) Azasetron Batanopride Bemesetron (MDL-72222) Bupropion Cilansetron CSP-2503 Dazopride Dolasetron Galanolactone Granisetron Hydroxybupropion Lerisetron Memantine Ondansetron Palonosetron Ramosetron Renzapride Ricasetron Tedatioxetine Tetracyclic antidepressants (e.g., amoxapine, mianserin, mirtazapine) Thujone Tropanserin Tropisetron Typical antipsychotics (e.g., loxapine) Volatiles/gases (e.g., nitrous oxide, sevoflurane, xenon) Vortioxetine Zacopride Zatosetron
Unknown/unsorted: LY-53857 Piperazines (e.g., naphthylpiperazine)

5-HT₄

Agonists: 5-MT BIMU8 Capeserod Cinitapride Cisapride CJ-033466 Dazopride Metoclopramide Minesapride Mosapride Prucalopride PRX-03140 Renzapride RS-67,333 RS-67,506 Serotonin (5-HT) Tegaserod Usmarapride Velusetrag Zacopride
Antagonists: GR-113808 GR-125487 L-Lysine Piboserod RS-39604 RS-67532 SB-203186 SB-204070

5-HT_5A

Agonists: Ergolines (e.g., 2-Br-LSD (BOL-148), ergotamine, LSD) Serotonin (5-HT) Tryptamines (e.g., 5-CT) Valerenic acid
Antagonists: Asenapine Latrepirdine (dimebolin) Metitepine (methiothepin) Ritanserin SB-699551 Unknown/unsorted: Ergolines (e.g., metergoline, methysergide) Piperazines (e.g., naphthylpiperazine)

5-HT₆

Agonists: Ergolines (e.g., dihydroergocryptine, dihydroergotamine, ergotamine, lisuride, LSD, mesulergine, metergoline, methysergide) Hypidone Serotonin (5-HT) Tryptamines (e.g., 2-Me-5-HT, 5-BT, 5-CT, 5-MT, Bufotenin, E-6801, E-6837, EMD-386088, EMDT, LY-586713, N-Me-5-HT, ST-1936, tryptamine) WAY-181187 WAY-208466
Antagonists: ABT-354 Atypical antipsychotics (e.g., aripiprazole, asenapine, clorotepine, clozapine, fluperlapine, iloperidone, olanzapine, tiospirone) AVN-101 AVN-211 AVN-322 AVN-397 BGC20-760 BVT-5182 BVT-74316 Cerlapirdine EGIS-12,233 GW-742457 Idalopirdine Ketanserin Landipirdine Latrepirdine (dimebolin) Masupirdine Metitepine (methiothepin) MS-245 PRX-07034 Ritanserin Ro 04-6790 Ro 63-0563 SB-258585 SB-271046 SB-357134 SB-399885 SB-742457 Tetracyclic antidepressants (e.g., amoxapine, mianserin) Tricyclic antidepressants (e.g., amitriptyline, clomipramine, doxepin, nortriptyline) Typical antipsychotics (e.g., chlorpromazine, loxapine)
Unknown/unsorted: Ergolines (e.g., 2-Br-LSD (BOL-148), bromocriptine, lergotrile, pergolide) Piperazines (e.g., naphthylpiperazine)

5-HT₇

Agonists: 8-OH-DPAT AS-19 Bifeprunox E-55888 Ergolines (e.g., LSD) LP-12 LP-44 LP-211 RU-24,969 Sarizotan Serotonin (5-HT) Triptans (e.g., frovatriptan) Tryptamines (e.g., 5-CT, 5-MT, bufotenin, N-Me-5-HT)
Antagonists: Atypical antipsychotics (e.g., amisulpride, aripiprazole, asenapine, brexpiprazole, clorotepine, clozapine, fluperlapine, olanzapine, risperidone, sertindole, tiospirone, ziprasidone, zotepine) Butaclamol DR-4485 EGIS-12,233 Ergolines (e.g., 2-Br-LSD (BOL-148), amesergide, bromocriptine, cabergoline, dihydroergotamine, ergotamine, LY-53857, LY-215,840, mesulergine, metergoline, methysergide, sergolexole) JNJ-18038683 Ketanserin LY-215,840 Metitepine (methiothepin) Ritanserin SB-258719 SB-258741 SB-269970 SB-656104 SB-656104A SB-691673 SLV-313 SLV-314 Spiperone SSR-181507 Tetracyclic antidepressants (e.g., amoxapine, maprotiline, mianserin, mirtazapine) Tricyclic antidepressants (e.g., amitriptyline, clomipramine, imipramine) Typical antipsychotics (e.g., acetophenazine, chlorpromazine, chlorprothixene, fluphenazine, loxapine, pimozide) Vortioxetine
Unknown/unsorted: Ergolines (e.g., lisuride, pergolide) Piperazines (e.g., naphthylpiperazine)

See also: Receptor/signaling modulators
Adrenergics
Dopaminergics
Melatonergics
Monoamine reuptake inhibitors and releasing agents
Monoamine metabolism modulators
Monoamine neurotoxins

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This page was last edited on 25 January 2023, at 23:32

Piromelatine

From Wikipedia, the free encyclopedia

See also

References