melatonin Indications/Contra | FAERs-F | FAERs-M | Orange Bk | BioActivity |

Stem definitionDrug idCAS RN
1672 73-31-4

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • melatonin
  • melatol
  • melatonine
  • circadin
A biogenic amine that is found in animals and plants. In mammals, melatonin is produced by the PINEAL GLAND. Its secretion increases in darkness and decreases during exposure to light. Melatonin is implicated in the regulation of SLEEP, mood, and REPRODUCTION. Melatonin is also an effective antioxidant.
  • Molecular weight: 232.28
  • Formula: C13H16N2O2
  • CLOGP: 1.03
  • LIPINSKI: 0
  • HAC: 4
  • HDO: 2
  • TPSA: 54.12
  • ALOGS: -3.21
  • ROTB: 4

Drug dosage:

DoseUnitRoute
2 mg O

ADMET properties:

PropertyValueReference
BDDCS (Biopharmaceutical Drug Disposition Classification System) 1 Benet LZ, Broccatelli F, Oprea TI
S (Water solubility) 0.10 mg/mL Benet LZ, Broccatelli F, Oprea TI
MRTD (Maximum Recommended Therapeutic Daily Dose) 0.36 ┬ÁM/kg/day Contrera JF, Matthews EJ, Kruhlak NL, Benz RD
BA (Bioavailability) 12 % Kim MT, Sedykh A, Chakravarti SK, Saiakhov RD, Zhu H
Vd (Volume of distribution) 1.10 L/kg Lombardo F, Berellini G, Obach RS
CL (Clearance) 16.50 mL/min/kg Lombardo F, Berellini G, Obach RS
fu (Fraction unbound in plasma) 0.39 % Lombardo F, Berellini G, Obach RS
t_half (Half-life) 1.10 hours Lombardo F, Berellini G, Obach RS

Approvals:

DateAgencyCompanyOrphan
None FDA
March 25, 2020 PMDA Nobelpharma Co., Ltd

FDA Adverse Event Reporting System (Female)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Intentional self-injury 454.53 10.95 257 33180 23909 46628716
Intentional overdose 342.85 10.95 319 33118 64625 46588000
Pneumonia aspiration 193.71 10.95 169 33268 31436 46621189
Somnolence 161.44 10.95 350 33087 156171 46496454
Gastrooesophageal reflux disease 127.67 10.95 207 33230 74137 46578488
Coma 114.82 10.95 173 33264 58176 46594449
Insomnia 87.24 10.95 288 33149 164636 46487989
Rheumatoid arthritis 64.29 10.95 47 33390 240168 46412457
Cestode infection 49.56 10.95 15 33422 272 46652353
Contraindicated product administered 45.46 10.95 3 33434 79944 46572681
Lip pruritus 44.66 10.95 16 33421 500 46652125
Fatigue 43.09 10.95 642 32795 608055 46044570
Premenstrual syndrome 40.52 10.95 16 33421 657 46651968
Magnesium deficiency 39.06 10.95 14 33423 438 46652187
Lichen sclerosus 35.42 10.95 16 33421 921 46651704
Desmoplastic small round cell tumour 34.81 10.95 10 33427 150 46652475
Sleep disorder 34.47 10.95 92 33345 46703 46605922
Disturbance in attention 34.06 10.95 72 33365 31488 46621137
Maternal exposure during pregnancy 33.11 10.95 16 33421 102533 46550092
Menstruation delayed 32.52 10.95 18 33419 1602 46651023
Onychoclasis 32.48 10.95 28 33409 5116 46647509
Polymenorrhoea 32.08 10.95 16 33421 1150 46651475
Exposure during pregnancy 31.84 10.95 19 33418 108193 46544432
Drug hypersensitivity 31.54 10.95 81 33356 243744 46408881
Hallucination 29.78 10.95 91 33346 49860 46602765
Irritability 28.90 10.95 64 33373 28882 46623743
Body temperature fluctuation 27.88 10.95 17 33420 1813 46650812
Treatment failure 27.87 10.95 16 33421 93071 46559554
Derailment 27.53 10.95 7 33430 64 46652561
Electrocardiogram PR prolongation 27.30 10.95 12 33425 647 46651978
Restless legs syndrome 26.99 10.95 44 33393 15799 46636826
Constipation 26.95 10.95 215 33222 173882 46478743
Suicidal ideation 26.70 10.95 95 33342 56287 46596338
Sleep apnoea syndrome 25.53 10.95 52 33385 22149 46630476
Helplessness 23.54 10.95 8 33429 213 46652412
Tachycardia 23.14 10.95 136 33301 99486 46553139
Seizure 23.03 10.95 159 33278 122895 46529730
Akathisia 22.98 10.95 28 33409 7686 46644939
Abnormal dreams 22.39 10.95 32 33405 10247 46642378
Suicide attempt 22.13 10.95 88 33349 54948 46597677
Staphylococcal scalded skin syndrome 21.99 10.95 7 33430 151 46652474
Tumour marker abnormal 21.48 10.95 7 33430 163 46652462
Tremor 21.39 10.95 149 33288 115490 46537135
Drug ineffective 20.91 10.95 351 33086 677487 45975138
Joint swelling 20.82 10.95 56 33381 166017 46486608
Restlessness 20.66 10.95 52 33385 25472 46627153
Synovitis 20.53 10.95 9 33428 61066 46591559
Abnormal behaviour 20.39 10.95 46 33391 21012 46631613
Acute kidney injury 19.91 10.95 94 33343 235761 46416864
General physical health deterioration 19.55 10.95 33 33404 115736 46536889
Renal failure 18.62 10.95 33 33404 113561 46539064
Feeling abnormal 18.55 10.95 153 33284 124907 46527718
Urine leukocyte esterase positive 18.49 10.95 15 33422 2520 46650105
Attention deficit hyperactivity disorder 18.32 10.95 14 33423 2158 46650467
Parasitic gastroenteritis 17.99 10.95 4 33433 19 46652606
Anxiety 17.82 10.95 204 33233 181753 46470872
Depression 17.70 10.95 193 33244 169911 46482714
Creatinine urine decreased 17.61 10.95 6 33431 161 46652464
Vision blurred 17.35 10.95 107 33330 79601 46573024
Skin burning sensation 17.28 10.95 29 33408 10663 46641962
Agitation 17.22 10.95 82 33355 55333 46597292
Rabbit syndrome 17.10 10.95 7 33430 316 46652309
Respiratory syncytial virus infection 16.81 10.95 19 33418 4816 46647809
Protrusion tongue 16.79 10.95 7 33430 331 46652294
Sinus bradycardia 16.71 10.95 33 33404 13749 46638876
Interstitial lung disease 16.54 10.95 9 33428 53940 46598685
Infusion site scar 16.32 10.95 6 33431 202 46652423
Convulsive threshold lowered 16.15 10.95 7 33430 365 46652260
Depressed level of consciousness 15.97 10.95 72 33365 47497 46605128
Metastases to peritoneum 15.89 10.95 14 33423 2634 46649991
Systemic lupus erythematosus 15.84 10.95 14 33423 65166 46587459
Coagulation factor V level increased 15.79 10.95 3 33434 5 46652620
Nightmare 15.79 10.95 36 33401 16562 46636063
Neuralgia 15.70 10.95 42 33395 21341 46631284
Vascular stent thrombosis 15.65 10.95 9 33428 862 46651763
Tri-iodothyronine free decreased 15.61 10.95 6 33431 229 46652396
Myocardial infarction 15.38 10.95 29 33408 97499 46555126
Multiple organ dysfunction syndrome 15.32 10.95 9 33428 51701 46600924
Band sensation 14.86 10.95 8 33429 674 46651951
Gingival pain 14.79 10.95 20 33417 6083 46646542
Weight increased 14.60 10.95 181 33256 164292 46488333
Merycism 14.48 10.95 5 33432 140 46652485
Cognitive disorder 14.05 10.95 58 33379 36825 46615800
Blepharospasm 13.60 10.95 12 33425 2262 46650363
Hepatic function abnormal 13.39 10.95 4 33433 34417 46618208
Memory impairment 13.33 10.95 98 33339 77239 46575386
Foetal exposure during pregnancy 13.05 10.95 3 33434 30744 46621881
Lactose intolerance 13.00 10.95 12 33425 2397 46650228
Sedation 12.96 10.95 41 33396 22869 46629756
Psychomotor hyperactivity 12.86 10.95 24 33413 9589 46643036
Snoring 12.78 10.95 14 33423 3428 46649197
Oculogyric crisis 12.78 10.95 9 33428 1224 46651401
Glossodynia 12.75 10.95 8 33429 44365 46608260
Drug intolerance 12.75 10.95 58 33379 146991 46505634
Anticonvulsant drug level decreased 12.71 10.95 9 33428 1235 46651390
Obstruction 12.69 10.95 10 33427 1612 46651013
Arthropathy 12.65 10.95 26 33411 84674 46567951
Alcoholic pancreatitis 12.50 10.95 3 33434 21 46652604
Confusional arousal 12.36 10.95 4 33433 91 46652534
Infusion site rash 12.21 10.95 8 33429 967 46651658
Activation syndrome 12.11 10.95 5 33432 231 46652394
Infusion site pruritus 12.07 10.95 13 33424 3125 46649500
Hypersomnia 12.02 10.95 31 33406 15408 46637217
Product administered to patient of inappropriate age 11.86 10.95 12 33425 2684 46649941
Balance disorder 11.84 10.95 83 33354 64438 46588187
Oral cavity fistula 11.76 10.95 7 33430 715 46651910
Water intoxication 11.73 10.95 6 33431 455 46652170
Sinus disorder 11.62 10.95 32 33405 16531 46636094
Chronic sinusitis 11.45 10.95 16 33421 5017 46647608
Sensation of foreign body 11.33 10.95 14 33423 3897 46648728
Crying 11.21 10.95 37 33400 21104 46631521

FDA Adverse Event Reporting System (Male)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Intentional self-injury 141.75 12.33 95 18996 13437 29919950
Hallucination 75.58 12.33 122 18969 48937 29884450
Parasomnia 68.96 12.33 19 19072 275 29933112
Appendicolith 62.02 12.33 23 19068 896 29932491
Aggression 59.87 12.33 94 18997 36813 29896574
Agitation 57.01 12.33 114 18977 53959 29879428
Insomnia 48.43 12.33 150 18941 93186 29840201
Intentional overdose 46.79 12.33 90 19001 41391 29891996
Dystonia 44.59 12.33 42 19049 9685 29923702
Choreoathetosis 43.80 12.33 18 19073 925 29932462
Fall 35.25 12.33 217 18874 181655 29751732
Abnormal sleep-related event 35.18 12.33 13 19078 501 29932886
Somnolence 34.97 12.33 138 18953 96625 29836762
Suicidal behaviour 31.50 12.33 16 19075 1346 29932041
Victim of child abuse 30.10 12.33 10 19081 280 29933107
Product administered to patient of inappropriate age 29.40 12.33 19 19072 2524 29930863
Confusional state 29.39 12.33 166 18925 134668 29798719
Abnormal behaviour 28.15 12.33 55 19036 25568 29907819
Tardive dyskinesia 27.42 12.33 24 19067 5033 29928354
Hallucinations, mixed 27.35 12.33 18 19073 2465 29930922
Appendicitis 27.15 12.33 26 19065 6118 29927269
Abdominal distension 24.17 12.33 74 19017 45635 29887752
Multiple drug therapy 23.59 12.33 8 19083 239 29933148
Electrocardiogram QT interval abnormal 22.51 12.33 6 19085 76 29933311
Drooling 22.04 12.33 17 19074 2988 29930399
Subacute cutaneous lupus erythematosus 21.84 12.33 10 19081 669 29932718
Constipation 21.37 12.33 134 18957 112772 29820615
Extrapyramidal disorder 21.29 12.33 30 19061 10663 29922724
Pleurothotonus 20.74 12.33 11 19080 1012 29932375
Behaviour disorder 20.71 12.33 15 19076 2397 29930990
Child abuse 20.48 12.33 7 19084 214 29933173
Respiratory alkalosis 20.13 12.33 12 19079 1382 29932005
Hypersomnia 19.99 12.33 30 19061 11286 29922101
Opisthotonus 19.86 12.33 8 19083 390 29932997
Suicidal ideation 19.59 12.33 59 19032 36055 29897332
Gastric hypomotility 18.86 12.33 5 19086 62 29933325
Acute kidney injury 18.43 12.33 101 18990 273741 29659646
Dyskinesia 18.33 12.33 42 19049 21792 29911595
Tic 18.28 12.33 13 19078 2019 29931368
Muscle rigidity 17.83 12.33 27 19064 10234 29923153
Seizure 17.47 12.33 115 18976 98360 29835027
Abscess intestinal 17.35 12.33 11 19080 1414 29931973
Hospice care 16.28 12.33 17 19074 4435 29928952
Psychomotor hyperactivity 16.26 12.33 23 19068 8201 29925186
Mental status changes 15.97 12.33 56 19035 37023 29896364
Poor quality sleep 15.44 12.33 21 19070 7220 29926167
Viral diarrhoea 15.40 12.33 5 19086 130 29933257
Myocardial infarction 15.34 12.33 36 19055 125589 29807798
Hepatic function abnormal 15.15 12.33 4 19087 41941 29891446
Interstitial lung disease 14.94 12.33 10 19081 60187 29873200
Stress 14.91 12.33 37 19054 20198 29913189
Salivary hypersecretion 14.73 12.33 21 19070 7545 29925842
Crying 14.68 12.33 18 19073 5591 29927796
Acute myocardial infarction 14.25 12.33 8 19083 52931 29880456
Eye movement disorder 14.24 12.33 15 19076 3953 29929434
Renal impairment 13.95 12.33 20 19071 84164 29849223
Arrhythmia supraventricular 13.89 12.33 9 19082 1201 29932186
Hyperkalaemia 13.83 12.33 13 19078 65997 29867390
Cardiogenic shock 13.68 12.33 32 19059 16829 29916558
Ear infection 13.67 12.33 20 19071 7354 29926033
Blood growth hormone increased 13.33 12.33 5 19086 201 29933186
Restlessness 13.28 12.33 38 19053 22561 29910826
Bladder dilatation 13.22 12.33 9 19082 1303 29932084
Dysarthria 13.09 12.33 46 19045 30444 29902943
Oculogyric crisis 12.84 12.33 9 19082 1366 29932021
Conjunctival discolouration 12.73 12.33 3 19088 22 29933365
Middle insomnia 12.70 12.33 17 19074 5756 29927631
Congenital hepatomegaly 12.39 12.33 3 19088 25 29933362
Fatigue 12.36 12.33 279 18812 320394 29612993
Precocious puberty 12.36 12.33 4 19087 103 29933284
Delirium 12.35 12.33 55 19036 40576 29892811

Pharmacologic Action:

SourceCodeDescription
ATC N05CH01 NERVOUS SYSTEM
PSYCHOLEPTICS
HYPNOTICS AND SEDATIVES
Melatonin receptor agonists
MeSH PA D000975 Antioxidants
MeSH PA D002491 Central Nervous System Agents
MeSH PA D002492 Central Nervous System Depressants
MeSH PA D020011 Protective Agents
CHEBI has role CHEBI:24621 hormones
CHEBI has role CHEBI:35488 cns depressants
CHEBI has role CHEBI:35623 antiepileptic
CHEBI has role CHEBI:48578 free-radical scavenger
CHEBI has role CHEBI:50847 immunostimulant
CHEBI has role CHEBI:75771 mus musculus metabolite
CHEBI has role CHEBI:77746 h. sapiens metabolites

Drug Use (View source of the data)

DiseaseRelationSNOMED_IDDOID
Disorders of initiating and maintaining sleep indication 194437008
Alcoholism contraindication 7200002
Psoriasis contraindication 9014002 DOID:8893
Poisoning by digitalis glycoside contraindication 12876009
Constipation contraindication 14760008 DOID:2089
Sarcoidosis contraindication 31541009 DOID:11335
Depressive disorder contraindication 35489007
Systemic lupus erythematosus contraindication 55464009 DOID:9074
Schizophrenia contraindication 58214004 DOID:5419
Hepatic failure contraindication 59927004
Hypercalcemia contraindication 66931009 DOID:12678
Poisoning by acetaminophen contraindication 70273001
Hypercalciuria contraindication 71938000
Autoimmune disease contraindication 85828009
Kidney disease contraindication 90708001 DOID:557
Eosinophilia myalgia syndrome contraindication 95416007 DOID:998
Kidney stone contraindication 95570007
Disease of liver contraindication 235856003 DOID:409

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 13.29 acidic
pKa2 13.99 acidic

Orange Book patent data (new drug applications)

None

Orange Book exclusivity data (new drug applications)

None

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])
Mechanism
action
Bioact sourceMoA source
Melatonin receptor type 1B GPCR AGONIST EC50 9.70 WOMBAT-PK IUPHAR
Melatonin receptor type 1A GPCR AGONIST EC50 9.40 WOMBAT-PK IUPHAR
5-hydroxytryptamine receptor 2B GPCR ANTAGONIST Ki 5.20 IUPHAR
Nuclear receptor ROR-alpha Nuclear hormone receptor EC50 9 WOMBAT-PK
Ribosyldihydronicotinamide dehydrogenase [quinone] Enzyme Ki 7.56 CHEMBL
Melatonin receptor GPCR Ki 9.75 CHEMBL
Melatonin receptor type 1B GPCR Ki 9.15 CHEMBL

External reference:

IDSource
4021324 VUID
N0000148757 NUI
4021324 VANDF
C1710381 UMLSCUI
CHEBI:16796 CHEBI
ML1 PDB_CHEM_ID
CHEMBL45 ChEMBL_ID
D008550 MESH_DESCRIPTOR_UI
DB01065 DRUGBANK_ID
896 PUBCHEM_CID
224 IUPHAR_LIGAND_ID
JL5DK93RCL UNII
6711 RXNORM
5037 MMSL
5609 MMSL
d04058 MMSL
005039 NDDF
116523008 SNOMEDCT_US
41199001 SNOMEDCT_US

Pharmaceutical products:

None