Nortriptyline (CHEM002216)

IdentificationTaxonomyBiological PropertiesPhysical PropertiesToxicity ProfileSpectraConcentrationsLinksReferencesTargets (24)XML
Record Information
Version1.0
Creation Date2009-07-21 20:27:06 UTC
Update Date2026-03-31 19:06:55 UTC
Accession NumberCHEM002216
Identification
Common NameNortriptyline
ClassSmall Molecule
DescriptionNortriptyline hydrochloride, the N-demethylated active metabolite of amitriptyline, is a dibenzocycloheptene-derivative tricyclic antidepressant (TCA). TCAs are structurally similar to phenothiazines. They contain a tricyclic ring system with an alkyl amine substituent on the central ring. In non-depressed individuals, nortriptyline does not affect mood or arousal, but may cause sedation. In depressed individuals, nortriptyline exerts a positive effect on mood. TCAs are potent inhibitors of serotonin and norepinephrine reuptake. Secondary amine TCAs, such as nortriptyline, are more potent inhibitors of norepinephrine reuptake than tertiary amine TCAs, such as amitriptyline. TCAs also down-regulate cerebral cortical β-adrenergic receptors and sensitize post-synaptic serotonergic receptors with chronic use. The antidepressant effects of TCAs are thought to be due to an overall increase in serotonergic neurotransmission. TCAs also block histamine-H1 receptors, α1-adrenergic receptors and muscarinic receptors, which accounts for their sedative, hypotensive and anticholinergic effects (e.g. blurred vision, dry mouth, constipation, urinary retention), respectively. See toxicity section below for a complete listing of side effects. Nortriptyline exerts less anticholinergic and sedative side effects compared to the tertiary amine TCAs, amitriptyline and clomipramine. Nortriptyline may be used to treat depression, chronic pain (unlabeled use), irritable bowel syndrome (unlabeled use), diabetic neuropathy (unlabeled use), post-traumatic stress disorder (unlabeled use), and for migraine prophylaxis (unlabeled use).
Contaminant Sources
  • HMDB Contaminants - Urine
  • STOFF IDENT Compounds
  • Suspected Compounds
  • T3DB toxins
Contaminant Type
  • Adrenergic Uptake Inhibitor
  • Amine
  • Antidepressant
  • Antidepressive Agent
  • Antidepressive Agent, Tricyclic
  • Drug
  • Metabolite
  • Norepinephrine Reuptake Inhibitor
  • Organic Compound
  • Synthetic Compound
Chemical Structure
Thumb
MOLSDF3D-SDFPDBSMILESInChI View 3D Structure
Synonyms
ValueSource
10,11-Dihydro-N-methyl-5H-dibenzo[a,D]cycloheptene-Delta(5,gamma)-propylamineChEBI
3-(10,11-Dihydro-5H-dibenzo[a,D]cyclohepten-5-ylidene)-N-methyl-1-propanamineChEBI
AtebenChEBI
AvantylChEBI
AventylChEBI
DemethylamitriptylineChEBI
DesmethylamitriptylineChEBI
NoritrenChEBI
NortriptylinaChEBI
NortriptylinumChEBI
PsychostylChEBI
SensavalChEBI
NortrilenKegg
10,11-Dihydro-N-methyl-5H-dibenzo[a,D]cycloheptene-delta(5,g)-propylamineGenerator
10,11-Dihydro-N-methyl-5H-dibenzo[a,D]cycloheptene-δ(5,γ)-propylamineGenerator
10,11-Dihydro-N-methyl-5H-dibenzo[a,D]cycloheptene-δ(5,g)-propylamineHMDB
Apo nortriptylineHMDB
DesmethylamitriptylinHMDB
Gen nortriptylineHMDB
Lundbeck brand OF nortriptyline hydrochlorideHMDB
Novo nortriptylineHMDB
Novopharm brand OF nortriptyline hydrochlorideHMDB
Reig jofre brand OF nortriptyline hydrochlorideHMDB
Apotex brand OF nortriptyline hydrochlorideHMDB
Genpharm brand OF nortriptyline hydrochlorideHMDB
Hydrochloride, nortriptylineHMDB
Nortriptyline hydrochlorideHMDB
Novo-nortriptylineHMDB
PMS-NortriptylineHMDB
Ratio nortriptylineHMDB
AllegronHMDB
Apo-nortriptylineHMDB
Dista brand OF nortriptyline hydrochlorideHMDB
Gen-nortriptylineHMDB
Lilly brand OF nortriptyline hydrochlorideHMDB
Nu-pharm brand OF nortriptyline hydrochlorideHMDB
PMS NortriptylineHMDB
PamelorHMDB
Pharmascience brand OF nortriptyline hydrochlorideHMDB
DesitriptylineHMDB
Mallinckrodt brand OF nortriptyline hydrochlorideHMDB
NorfenazinHMDB
Nu nortriptylineHMDB
Nu pharm brand OF nortriptyline hydrochlorideHMDB
Nu-nortriptylineHMDB
PaxtibiHMDB
Ratiopharm brand OF nortriptyline hydrochlorideHMDB
Ratio-nortriptylineHMDB
Chemical FormulaC19H21N
Average Molecular Mass263.377 g/mol
Monoisotopic Mass263.167 g/mol
CAS Registry Number72-69-5
IUPAC Namemethyl(3-{tricyclo[9.4.0.0³,⁸]pentadeca-1(15),3,5,7,11,13-hexaen-2-ylidene}propyl)amine
Traditional Namenortriptyline
SMILESCNCCC=C1C2=CC=CC=C2CCC2=CC=CC=C12
InChI IdentifierInChI=1S/C19H21N/c1-20-14-6-11-19-17-9-4-2-7-15(17)12-13-16-8-3-5-10-18(16)19/h2-5,7-11,20H,6,12-14H2,1H3
InChI KeyPHVGLTMQBUFIQQ-UHFFFAOYSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as dibenzocycloheptenes. Dibenzocycloheptenes are compounds containing a dibenzocycloheptene moiety, which consists of two benzene rings connected by a cycloheptene ring.
KingdomOrganic compounds
Super ClassBenzenoids
ClassDibenzocycloheptenes
Sub ClassNot Available
Direct ParentDibenzocycloheptenes
Alternative Parents
Substituents
  • Dibenzocycloheptene
  • Secondary amine
  • Secondary aliphatic amine
  • Organic nitrogen compound
  • Organopnictogen compound
  • Hydrocarbon derivative
  • Organonitrogen compound
  • Amine
  • Aromatic homopolycyclic compound
Molecular FrameworkAromatic homopolycyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Cytoplasm
  • Extracellular
  • Membrane
Biofluid LocationsNot Available
Tissue Locations
  • Kidney
  • Liver
PathwaysNot Available
Applications
Biological Roles
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting Point213-215°C
Boiling PointNot Available
Solubility8.74e-04 g/L
Predicted Properties
PropertyValueSource
Water Solubility0.00087 g/LALOGPS
logP4.65ALOGPS
logP4.43ChemAxon
logS-5.5ALOGPS
pKa (Strongest Basic)10.47ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count1ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area12.03 ŲChemAxon
Rotatable Bond Count3ChemAxon
Refractivity96.21 m³·mol⁻¹ChemAxon
Polarizability31.87 ųChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyView
GC-MSGC-MS Spectrum - EI-B (Non-derivatized)splash10-0006-9000000000-bb9eae4818c0402317eeSpectrum
GC-MSGC-MS Spectrum - EI-B (Non-derivatized)splash10-0006-9000000000-bb9eae4818c0402317eeSpectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-0006-9040000000-03aa30e0f3d1715d991eSpectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, PositiveNot AvailableSpectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, PositiveNot AvailableSpectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-05nf-5970000000-f92c7d23474b57a4ba50Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-03di-0090000000-4c40cb3ec4df8809981eSpectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-06sl-2590000000-be2abd28b2b0f75dd8bbSpectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-05mo-3940000000-6a454924ec75665c6175Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-05mo-3930000000-eb8141866b19782dd1e5Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-00kf-4930000000-81614e655fc32d5839ceSpectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-00kf-4930000000-f918306a99d07f887503Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-0gdl-5930000000-d876ab376d0e9885d06dSpectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-0gb9-5930000000-e51a246750bf8ce7e4ecSpectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-0gbi-5930000000-c2811578219a3a7e1ccfSpectrum
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-03yi-0490000000-094e7bdb831aed030f5fSpectrum
LC-MS/MSLC-MS/MS Spectrum - 75V, Positivesplash10-00kf-4930000000-fb69faeba7a357c5bc5aSpectrum
LC-MS/MSLC-MS/MS Spectrum - 90V, Positivesplash10-00kf-4930000000-76afa553a0a96ca36196Spectrum
LC-MS/MSLC-MS/MS Spectrum - 30V, Positivesplash10-06sl-2590000000-8294a4644460a638747bSpectrum
LC-MS/MSLC-MS/MS Spectrum - 15V, Positivesplash10-03di-0090000000-ff969015b0f97e8c78bcSpectrum
LC-MS/MSLC-MS/MS Spectrum - 45V, Positivesplash10-05mo-3940000000-2244b5f59802d5d17a11Spectrum
LC-MS/MSLC-MS/MS Spectrum - 60V, Positivesplash10-05mo-3930000000-ae25ca0dbf191a8decb7Spectrum
LC-MS/MSLC-MS/MS Spectrum - -1V, Positivesplash10-05nf-5970000000-279d8674cee6125e1363Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-03e9-1090000000-0122fb1ff7e4f061277fSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-01qc-3290000000-820f6bab951ae7e9352dSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0006-6950000000-d6a7a0dcc07c2ab8c35fSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-03di-0090000000-6586d2d06dd2491b85d0Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-03di-1090000000-3af72990a6e6a4c9e3abSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-001l-4290000000-05af30a36ff956182b21Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-03di-0090000000-0f92e6ab1c1e69d00ae5Spectrum
MSMass Spectrum (Electron Ionization)splash10-0006-9230000000-15f73e5232a0e230f41bSpectrum
Toxicity Profile
Route of ExposureOral, well absorbed from the GI tract. Peak plasma concentrations occur 7-8.5 hours following oral administration.
Mechanism of ToxicityIt is believed that nortriptyline either inhibits the reuptake of the neurotransmitter serotonin at the neuronal membrane or acts at beta-adrenergic receptors. Tricyclic antidepressants do not inhibit monoamine oxidase nor do they affect dopamine reuptake.
MetabolismUndergoes hepatic metabolism via the same pathway as other TCAs. Route of Elimination: Approximately one-third of a single orally administered dose is excreted in urine within 24 hours. Small amounts are excreted in feces via biliary elimination. Half Life: 16 to 90+ hours
Toxicity ValuesLD50=mg/kg (orally in rat)
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesFor the treatment of depression, chronic pain, irritable bowel syndrome, sleep disorders, diabetic neuropathy, agitation and insomnia, and migraine prophylaxis.
Minimum Risk LevelNot Available
Health EffectsNot Available
SymptomsSymptoms of overdose include cardiac dysrhythmias, severe hypotension, shock, congestive heart failure, pulmonary edema, convulsions, and CNS depression, including coma. Changes in the electrocardiogram, particularly in QRS axis or width, are clinically significant indicators of tricyclic antidepressant toxicity.
TreatmentNot Available
Concentrations
Not Available
DrugBank IDDB00540
HMDB IDHMDB0014680
FooDB IDNot Available
Phenol Explorer IDNot Available
KNApSAcK IDNot Available
BiGG IDNot Available
BioCyc IDNot Available
METLIN IDNot Available
PDB IDNot Available
Wikipedia LinkNortriptyline
Chemspider ID4384
ChEBI ID7640
PubChem Compound ID4543
Kegg Compound IDC07274
YMDB IDNot Available
ECMDB IDNot Available
References
Synthesis Reference

Abraham Nudelman, “ACID ADDITION SALT OF A NORTRIPTYLINE-GABA CONJUGATE AND A PROCESS OF PREPARING SAME.” U.S. Patent US20130184347, issued July 18, 2013.

MSDSNot Available
General References
1. Prochazka AV, Weaver MJ, Keller RT, Fryer GE, Licari PA, Lofaso D: A randomized trial of nortriptyline for smoking cessation. Arch Intern Med. 1998 Oct 12;158(18):2035-9.
2. https://www.ncbi.nlm.nih.gov/pubmed/?term=10379421
3. https://www.ncbi.nlm.nih.gov/pubmed/?term=14561440
4. https://www.ncbi.nlm.nih.gov/pubmed/?term=17071817
5. https://www.ncbi.nlm.nih.gov/pubmed/?term=23280809
6. https://www.ncbi.nlm.nih.gov/pubmed/?term=24037379
7. https://www.ncbi.nlm.nih.gov/pubmed/?term=24368464
8. https://www.ncbi.nlm.nih.gov/pubmed/?term=25224004
9. https://www.ncbi.nlm.nih.gov/pubmed/?term=25480462
10. https://www.ncbi.nlm.nih.gov/pubmed/?term=25569864
11. https://www.ncbi.nlm.nih.gov/pubmed/?term=25592638
12. https://www.ncbi.nlm.nih.gov/pubmed/?term=25683584
13. https://www.ncbi.nlm.nih.gov/pubmed/?term=25707462
14. https://www.ncbi.nlm.nih.gov/pubmed/?term=25749306
15. https://www.ncbi.nlm.nih.gov/pubmed/?term=26086857
16. https://www.ncbi.nlm.nih.gov/pubmed/?term=26453560