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

Stem definitionDrug idCAS RN
antidepressants, dibenzo[a,d]cycloheptane or cyclopheptene derivatives 1971 72-69-5

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • nortryptyline
  • nortriptyline
  • demethylamitriptylin
  • desitriptilina
  • desmethylamitriptyline
  • noramitriptyline
  • nortriptyline hydrochloride
  • nortriptyline HCl
A metabolite of AMITRIPTYLINE that is also used as an antidepressive agent. Nortriptyline is used in major depression, dysthymia, and atypical depressions.
  • Molecular weight: 263.38
  • Formula: C19H21N
  • CLOGP: 4.31
  • LIPINSKI: 0
  • HAC: 1
  • HDO: 1
  • TPSA: 12.03
  • ALOGS: -5.48
  • ROTB: 3

  • Status: OFP

  • Legend:
    OFP - off patent
    OFM - off market
    ONP - on patent

Drug dosage:

DoseUnitRoute
75 mg O
30 mg P

ADMET properties:

PropertyValueReference
BDDCS (Biopharmaceutical Drug Disposition Classification System) 1 Benet LZ, Broccatelli F, Oprea TI
EoM (Fraction excreted unchanged in urine) 2 % Benet LZ, Broccatelli F, Oprea TI
MRTD (Maximum Recommended Therapeutic Daily Dose) 6.34 ┬ÁM/kg/day Contrera JF, Matthews EJ, Kruhlak NL, Benz RD
BA (Bioavailability) 51 % Kim MT, Sedykh A, Chakravarti SK, Saiakhov RD, Zhu H
Vd (Volume of distribution) 22 L/kg Lombardo F, Berellini G, Obach RS
CL (Clearance) 10 mL/min/kg Lombardo F, Berellini G, Obach RS
fu (Fraction unbound in plasma) 0.12 % Lombardo F, Berellini G, Obach RS
t_half (Half-life) 30 hours Lombardo F, Berellini G, Obach RS

Approvals:

DateAgencyCompanyOrphan
Nov. 6, 1964 FDA

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
Completed suicide 1090.07 48.01 256 963 20778 2336088
Toxicity to various agents 908.81 48.01 242 977 32512 2324354
Drug hypersensitivity 510.09 48.01 169 1050 46474 2310392
Pneumonia aspiration 443.48 48.01 91 1128 3651 2353215
Coma 363.41 48.01 91 1128 8965 2347901
Somnolence 344.24 48.01 107 1112 23378 2333488
Gastrooesophageal reflux disease 343.03 48.01 87 1132 9008 2347858
Cardiac arrest 260.52 48.01 78 1141 14852 2342014
Overdose 242.49 48.01 79 1140 19828 2337038
Temperature regulation disorder 230.28 48.01 33 1186 128 2356738
Food allergy 185.23 48.01 33 1186 598 2356268
Cardio-respiratory arrest 181.90 48.01 53 1166 9093 2347773
Coeliac disease 176.12 48.01 33 1186 799 2356067
Immunodeficiency 167.65 48.01 33 1186 1043 2355823
Intentional overdose 158.14 48.01 50 1169 11271 2345595
Bursitis 154.34 48.01 34 1185 1874 2354992
Drug abuse 142.94 48.01 47 1172 11979 2344887
Respiratory arrest 132.42 48.01 38 1181 6140 2350726
Hypotension 116.39 48.01 53 1166 32383 2324483
Fluid retention 114.54 48.01 35 1184 7011 2349855
Rash erythematous 111.41 48.01 33 1186 5943 2350923
Hepatic enzyme increased 111.12 48.01 37 1182 9765 2347101
Asthma 109.78 48.01 38 1181 11276 2345590
Constipation 109.15 48.01 45 1174 21584 2335282
Electrocardiogram QRS complex prolonged 107.93 48.01 23 1196 1079 2355787
Upper respiratory tract infection 102.65 48.01 34 1185 8817 2348049
Hypersensitivity 98.77 48.01 43 1176 23550 2333316
Hyperhidrosis 98.30 48.01 38 1181 15384 2341482
Delirium 98.02 48.01 29 1190 5194 2351672
Drug ineffective 97.69 48.01 70 1149 101554 2255312
Accidental overdose 92.08 48.01 26 1193 3946 2352920
Death 89.54 48.01 61 1158 81407 2275459
Rheumatoid arthritis 83.69 48.01 36 1183 19104 2337762
Headache 83.27 48.01 58 1161 80121 2276745
Fatigue 82.60 48.01 59 1160 84814 2272052
Tachycardia 82.19 48.01 34 1185 16375 2340491
Poisoning 81.70 48.01 22 1197 2798 2354068
Back pain 80.77 48.01 41 1178 31618 2325248
Miosis 72.83 48.01 17 1202 1207 2355659
Erythema 71.25 48.01 35 1184 25124 2331742
Accidental death 69.63 48.01 13 1206 306 2356560
Suicidal ideation 69.42 48.01 27 1192 11060 2345806
Pain 69.39 48.01 47 1172 61810 2295056
Suicide attempt 65.44 48.01 26 1193 11256 2345610
Traumatic coma 65.17 48.01 8 1211 4 2356862
Electrocardiogram QT prolonged 63.34 48.01 23 1196 7791 2349075
Ventricular tachycardia 62.07 48.01 18 1201 2993 2353873
Long QT syndrome 62.03 48.01 13 1206 560 2356306
Seizure 60.31 48.01 31 1188 24435 2332431
Sedation 55.81 48.01 17 1202 3345 2353521
Condition aggravated 52.53 48.01 31 1188 31948 2324918
Hyperreflexia 50.89 48.01 12 1207 889 2355977
Psychotic disorder 50.28 48.01 17 1202 4662 2352204
Agitation 48.90 48.01 21 1198 11030 2345836

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
Toxicity to various agents 660.54 58.79 179 501 28962 1717139
Completed suicide 615.06 58.79 151 529 16161 1729940
Suicidal ideation 214.20 58.79 58 622 8460 1737641
Drug abuse 165.97 58.79 53 627 13636 1732465
Sedation 98.26 58.79 26 654 3391 1742710
Serotonin syndrome 83.87 58.79 22 658 2766 1743335
Electrocardiogram QRS complex prolonged 82.04 58.79 17 663 758 1745343
Overdose 81.16 58.79 33 647 16668 1729433
Cardio-respiratory arrest 80.27 58.79 28 652 9265 1736836
Respiratory depression 68.83 58.79 18 662 2229 1743872
Brugada syndrome 67.24 58.79 12 668 238 1745863
Drug hypersensitivity 63.62 58.79 27 653 15108 1730993

Pharmacologic Action:

SourceCodeDescription
ATC N06AA10 NERVOUS SYSTEM
PSYCHOANALEPTICS
ANTIDEPRESSANTS
Non-selective monoamine reuptake inhibitors
MeSH PA D018663 Adrenergic Agents
FDA EPC N0000175752 Tricyclic Antidepressant
MeSH PA D018759 Adrenergic Uptake Inhibitors
CHEBI has role CHEBI:35469 antidepressant
CHEBI has role CHEBI:35640 adrenergic uptake inhibitor
CHEBI has role CHEBI:35480 analgesic
CHEBI has role CHEBI:35610 antineoplastic agent
MeSH PA D000928 Antidepressive Agents
MeSH PA D000929 Antidepressive Agents, Tricyclic
MeSH PA D002491 Central Nervous System Agents
MeSH PA D049990 Membrane Transport Modulators
MeSH PA D018377 Neurotransmitter Agents
MeSH PA D014179 Neurotransmitter Uptake Inhibitors
MeSH PA D011619 Psychotropic Drugs

Drug Use (View source of the data)

DiseaseRelationSNOMED_IDDOID
Depressive disorder indication 35489007
Neuropathic pain off-label use 247398009
Smoking cessation assistance off-label use 384742004
Attention deficit hyperactivity disorder off-label use 406506008
Suicidal thoughts contraindication 6471006
Alcoholism contraindication 7200002
Sinus tachycardia contraindication 11092001
Lowered convulsive threshold contraindication 19260006
Myocardial infarction contraindication 22298006 DOID:5844
Glaucoma contraindication 23986001 DOID:1686
Torsades de pointes contraindication 31722008
Hyperthyroidism contraindication 34486009 DOID:7998
Renal failure syndrome contraindication 42399005 DOID:1074
Conduction disorder of the heart contraindication 44808001
Hepatic failure contraindication 59927004
Open-angle glaucoma contraindication 84494001 DOID:1067
Epilepsy contraindication 84757009 DOID:1826
Prolonged QT interval contraindication 111975006
Seizure disorder contraindication 128613002
Bipolar affective disorder, current episode manic contraindication 191618007
Cerebrovascular accident contraindication 230690007
Benign prostatic hyperplasia contraindication 266569009
Retention of urine contraindication 267064002
Non-Q wave myocardial infarction contraindication 314207007
Breastfeeding (mother) contraindication 413712001
Myocardial infarction in recovery phase contraindication 418044006
Congenital long QT syndrome contraindication 442917000

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 9.5 Basic

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
Sodium-dependent serotonin transporter Transporter INHIBITOR Ki 7.34 WOMBAT-PK CHEMBL
Sodium-dependent noradrenaline transporter Transporter INHIBITOR Kd 8.36 WOMBAT-PK CHEMBL
Alpha-2A adrenergic receptor GPCR Ki 6.56 DRUG MATRIX
5-hydroxytryptamine receptor 2B GPCR Ki 7.07 DRUG MATRIX
D(3) dopamine receptor GPCR Ki 7.21 DRUG MATRIX
Histamine H2 receptor GPCR Ki 5.64 DRUG MATRIX
Alpha-2C adrenergic receptor GPCR Ki 7.52 DRUG MATRIX
Alpha-1D adrenergic receptor GPCR Ki 6.91 DRUG MATRIX
Cytochrome P450 2C19 Enzyme IC50 5.52 DRUG MATRIX
5-hydroxytryptamine receptor 6 GPCR Ki 6.67 CHEMBL
Cytochrome P450 2D6 Enzyme Km 6.22 WOMBAT-PK
Aldehyde oxidase Enzyme IC50 6.07 WOMBAT-PK
Muscarinic acetylcholine receptor M5 GPCR Ki 7.01 WOMBAT-PK
Muscarinic acetylcholine receptor M4 GPCR Ki 7.08 WOMBAT-PK
Muscarinic acetylcholine receptor M3 GPCR Ki 7.30 WOMBAT-PK
Muscarinic acetylcholine receptor M2 GPCR Ki 6.96 WOMBAT-PK
Muscarinic acetylcholine receptor M1 GPCR Ki 7.40 WOMBAT-PK
Histamine H1 receptor GPCR Kd 8.03 WOMBAT-PK
Alpha-2B adrenergic receptor GPCR Ki 7 WOMBAT-PK
Alpha-1A adrenergic receptor GPCR Ki 7.26 WOMBAT-PK
5-hydroxytryptamine receptor 2C GPCR Ki 8 WOMBAT-PK
5-hydroxytryptamine receptor 2A GPCR Ki 7.36 WOMBAT-PK
5-hydroxytryptamine receptor 1A GPCR Ki 6.51 WOMBAT-PK
D(2) dopamine receptor GPCR Ki 5.59 PDSP
ATP-sensitive inward rectifier potassium channel 10 Ion channel BLOCKER IC50 4.80 SCIENTIFIC LITERATURE
Proto-oncogene tyrosine-protein kinase receptor Ret Kinase IC50 5.82 CHEMBL
Sodium-dependent dopamine transporter Transporter Ki 5.92 PDSP
D(1A) dopamine receptor GPCR Ki 6.57 DRUG MATRIX
Alpha-1B adrenergic receptor GPCR Ki 6.94 DRUG MATRIX
5-hydroxytryptamine receptor 1B GPCR Ki 5.84 DRUG MATRIX
Alpha-1A adrenergic receptor GPCR IC50 10.40 CHEMBL
Histamine H1 receptor GPCR IC50 10.30 CHEMBL
5-hydroxytryptamine receptor 1A GPCR IC50 5.73 CHEMBL

External reference:

IDSource
4019860 VUID
N0000147946 NUI
C0028420 UMLSCUI
D00816 KEGG_DRUG
00FN6IH15D UNII
894-71-3 SECONDARY_CAS_RN
13432000 SNOMEDCT_US
4019860 VANDF
2740 MMSL
7531 RXNORM
372652004 SNOMEDCT_US
d00144 MMSL
004601 NDDF
1328 INN_ID
CHEBI:7640 CHEBI
CHEMBL445 ChEMBL_ID
DB00540 DRUGBANK_ID
21B PDB_CHEM_ID
4543 PUBCHEM_CID
CHEMBL1201156 ChEMBL_ID
D009661 MESH_DESCRIPTOR_UI
2404 IUPHAR_LIGAND_ID

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
Nortriptyline Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 0093-0810 CAPSULE 10 mg ORAL ANDA 13 sections
Nortriptyline Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 0093-0811 CAPSULE 25 mg ORAL ANDA 13 sections
Nortriptyline Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 0093-0812 CAPSULE 50 mg ORAL ANDA 13 sections
Nortriptyline Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 0093-0813 CAPSULE 75 mg ORAL ANDA 13 sections
Nortriptyline Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 0121-0678 SOLUTION 10 mg ORAL ANDA 14 sections
PAMELOR HUMAN PRESCRIPTION DRUG LABEL 1 0406-9910 CAPSULE 10 mg ORAL NDA 13 sections
PAMELOR HUMAN PRESCRIPTION DRUG LABEL 1 0406-9911 CAPSULE 25 mg ORAL NDA 13 sections
PAMELOR HUMAN PRESCRIPTION DRUG LABEL 1 0406-9912 CAPSULE 50 mg ORAL NDA 13 sections
PAMELOR HUMAN PRESCRIPTION DRUG LABEL 1 0406-9913 CAPSULE 75 mg ORAL NDA 13 sections
Nortriptyline Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 10544-567 CAPSULE 10 mg ORAL ANDA 13 sections
NORTRIPTYLINE HYDROCHLORIDE HUMAN PRESCRIPTION DRUG LABEL 1 16590-171 CAPSULE 25 mg ORAL ANDA 13 sections
Nortriptyline Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 21695-093 CAPSULE 10 mg ORAL ANDA 13 sections
Nortriptyline Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 21695-094 CAPSULE 25 mg ORAL ANDA 13 sections
Nortriptyline Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 21695-599 CAPSULE 50 mg ORAL ANDA 13 sections
Nortriptyline Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 21695-600 CAPSULE 75 mg ORAL ANDA 13 sections
Nortriptyline Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 33261-348 CAPSULE 25 mg ORAL ANDA 13 sections
Nortriptyline Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 33261-532 CAPSULE 10 mg ORAL ANDA 13 sections
Nortriptyline Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 33261-692 CAPSULE 50 mg ORAL ANDA 13 sections
Nortriptyline Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 33261-804 CAPSULE 75 mg ORAL ANDA 13 sections
Nortriptyline Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 43063-722 CAPSULE 25 mg ORAL ANDA 14 sections
Nortriptyline Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 43063-897 CAPSULE 25 mg ORAL ANDA 14 sections
Nortriptyline Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 45865-371 CAPSULE 10 mg ORAL ANDA 14 sections
Nortriptyline Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 50090-0507 CAPSULE 25 mg ORAL ANDA 14 sections
Nortriptyline Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 50090-0537 CAPSULE 10 mg ORAL ANDA 14 sections
Nortriptyline Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 50268-603 CAPSULE 10 mg ORAL ANDA 13 sections
Nortriptyline Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 50268-604 CAPSULE 25 mg ORAL ANDA 13 sections
Nortriptyline Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 50268-605 CAPSULE 50 mg ORAL ANDA 13 sections
Nortriptyline Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 50436-4022 CAPSULE 25 mg ORAL ANDA 14 sections
Nortriptyline Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 50436-6652 CAPSULE 10 mg ORAL ANDA 13 sections
Nortriptyline Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 51672-4001 CAPSULE 10 mg ORAL ANDA 14 sections