U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ACHIRAL
Molecular Formula C19H21N
Molecular Weight 263.3767
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of NORTRIPTYLINE

SMILES

CNCCC=C1C2=C(CCC3=C1C=CC=C3)C=CC=C2

InChI

InChIKey=PHVGLTMQBUFIQQ-UHFFFAOYSA-N
InChI=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

HIDE SMILES / InChI

Molecular Formula C19H21N
Molecular Weight 263.3767
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Nortriptyline is a second-generation tricyclic antidepressant (TCA) marketed as the hydrochloride salt under the trade names Sensoval, Aventyl, Pamelor, Norpress, Allegron, Noritren and Nortrilen. Nortriptyline is used in the treatment of depression and childhood nocturnal enuresis. Its off-label uses include treatment of postherpetic neuralgia, angioedema and smoking Cessation, and attention deficit hyperactivity disorder in some neurological disorders. It is believed that nortriptyline either inhibits the reuptake of the neurotransmitter serotonin at the neuronal membrane or acts at beta-adrenergic receptors. Nortriptyline is US FDA-approved for the treatment of major depression. In the United Kingdom, it may also be used for treating nocturnal enuresis, with courses of treatment lasting no more than three months. The most common side effects include dry mouth, sedation, constipation, and increased appetite, mild blurred vision, tinnitus, occasionally hypomania or mania. An occasional side effect is a rapid or irregular heartbeat. Alcohol may exacerbate some of its side effects. However, fewer and milder side effects occur with nortriptyline than tertiary tricyclic antidepressants such as imipramine and amitriptyline. For this reason, nortriptyline is preferred to other tricyclic antidepressants, particularly with older adults, which also improves compliance.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
6.3 nM [Ki]
0.04 nM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Preventing
AVENTYL HYDROCHLORIDE

Approved Use

Nortriptyline hydrochloride capsules are indicated for the relief of symptoms of depression. Endogenous depressions are more likely to be alleviated than are other depressive states.

Launch Date

-1.62604794E11
Primary
AVENTYL HYDROCHLORIDE

Approved Use

Nortriptyline hydrochloride capsules are indicated for the relief of symptoms of depression. Endogenous depressions are more likely to be alleviated than are other depressive states.

Launch Date

-1.62604794E11
Primary
AVENTYL HYDROCHLORIDE

Approved Use

Nortriptyline hydrochloride capsules are indicated for the relief of symptoms of depression. Endogenous depressions are more likely to be alleviated than are other depressive states.

Launch Date

-1.62604794E11
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
36 nM
25 mg single, oral
dose: 25 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
NORTRIPTYLINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
16.91 ng/mL
25 mg single, oral
dose: 25 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
NORTRIPTYLINE plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
1591 nM × h
25 mg single, oral
dose: 25 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
NORTRIPTYLINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
767.28 ng × h/mL
25 mg single, oral
dose: 25 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
NORTRIPTYLINE plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
29.3 h
25 mg single, oral
dose: 25 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
NORTRIPTYLINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
32.75 h
25 mg single, oral
dose: 25 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
NORTRIPTYLINE plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
8.35%
NORTRIPTYLINE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG



OverviewOther

Other InhibitorOther SubstrateOther Inducer



Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
yes [Ki 450 uM]
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
major
likely (co-administration study)
Comment: Concomitant use of tricyclic antidepressants with drugs that can inhibit cytochrome P450 2D6 may require lower doses than usually prescribed for either the tricyclic antidepressant or the other drug
minor
minor
yes
Tox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
PubMed

PubMed

TitleDatePubMed
Amitriptyline and heart block.
1967 Jul 29
Correlation of subjective side effects with plasma concentrations of nortriptyline.
1970 Oct 3
Tricyclic antidepressants and monoamine oxidase inhibitors.
1971 Jun
Electrocardiographic changes and cardiac arrhythmias in patients receiving psychotropic drugs.
1976 Feb
[The extrapyramidal symptoms in the combination of lithium long-term lithium therapy with nortriptyline. A case report on the formation of a pathogenesis hypothesis].
1976 Jan
[Double blind clinical study of mianserin and nortriptyline (author's transl)].
1978 Sep-Oct
Hoarseness and aphonia as a side effect of tricyclic antidepressants.
1979 Dec
Cardiovascular side effects of long-term therapy with tricyclic antidepressants in the aged.
1979 May
Comparison of imipramine- and nortriptyline-induced orthostatic hypotension: a meaningful difference.
1981 Sep
Marked sinus tachycardia resulting from the synergistic effects of marijuana and nortriptyline.
1983 May
A placebo-controlled comparison of the effect of nortriptyline and phenelzine on orthostatic hypotension in elderly depressed patients.
1987 Dec
Tryptophan antagonism of stimulant-induced tics.
1989 Feb
Treatment-emergent depression with antidepressants in panic disorder.
1989 May-Jun
Naproxen reversal of nortriptyline-induced orthostatic hypotension.
1989 Sep
Simulated home treatment of depression with nortriptyline.
1991
Left bundle branch block developing in a patient with sub-therapeutic nortriptyline levels: a case report.
1991 Oct
Cognitive decline with nortriptyline use in a patient with dementia of the Alzheimer's type.
1992 Jan
High initial nortriptyline doses in the treatment of depression.
1993 Feb
Sleep in bereavement-related depression during and after pharmacotherapy with nortriptyline.
1994 Apr-Jun
Nortriptyline-induced fulminant hepatic failure.
1995 Jan
Mixed mania: apparent induction by a tricyclic antidepressant in five consecutively treated patients with bipolar depression.
1995 Jan 1
Depression following smoking cessation in women.
1996
Nortriptyline-induced hepatic failure.
1996 Feb
Extrapyramidal symptoms associated with the adjunct of nortriptyline to a venlafaxine-valproic acid combination.
1999 May
Penetration of amitriptyline, but not of fluoxetine, into brain is enhanced in mice with blood-brain barrier deficiency due to mdr1a P-glycoprotein gene disruption.
2000 Apr
Inhibition of cytochrome P4502D6 activity with paroxetine normalizes the ultrarapid metabolizer phenotype as measured by nortriptyline pharmacokinetics and the debrisoquin test.
2001 Oct
Risk factors for falls during treatment of late-life depression.
2002 Oct
The promises and pitfalls of reboxetine.
2003 Winter
Interactions of cyclobenzaprine and tricyclic antidepressants.
2005 Jan
Determination of the dissociation constants (pKa) of secondary and tertiary amines in organic media by capillary electrophoresis and their role in the electrophoretic mobility order inversion.
2005 Mar 11
Monoamine transporter gene polymorphisms and antidepressant response in koreans with late-life depression.
2006 Oct 4
In silico prediction of pregnane X receptor activators by machine learning approaches.
2007 Jan
Tobacco smoking cessation management: integrating varenicline in current practice.
2008
Nortriptyline protects mitochondria and reduces cerebral ischemia/hypoxia injury.
2008 Feb
Tako-tsubo syndrome following nortriptyline overdose.
2008 Jun
Possession states precipitated by nortriptyline.
2008 May
Bioactivation of the tricyclic antidepressant amitriptyline and its metabolite nortriptyline to arene oxide intermediates in human liver microsomes and recombinant P450s.
2008 May 9
Community-based randomised controlled trial evaluating falls and osteoporosis risk management strategies.
2008 Nov 4
Trifluoperazine: a rynodine receptor agonist.
2009 Aug
Spontaneous hypothermia on intensive care unit admission is a predictor of unfavorable neurological outcome in patients after resuscitation: an observational cohort study.
2010
Early-life stress and antidepressants modulate peripheral biomarkers in a gene-environment rat model of depression.
2010 Aug 16
Development of a list of potentially inappropriate drugs for the korean elderly using the delphi method.
2010 Dec
Current treatment options in smoking cessation.
2010 Feb
An overview of Indian research in anxiety disorders.
2010 Jan
Which xenobiotic(s) could be responsible for the radiologic findings below? Answer: any proconvulsant xenobiotic, in this case tramadol, bupropion, and nortriptyline.
2010 Mar
Profiling of a prescription drug library for potential renal drug-drug interactions mediated by the organic cation transporter 2.
2011 Jul 14
Palmitate increases the susceptibility of cells to drug-induced toxicity: an in vitro method to identify drugs with potential contraindications in patients with metabolic disease.
2012 Oct
Patents

Sample Use Guides

25mg PO q6-8hr. No more than 150 mg/day
Route of Administration: Oral
Two cell lines and eight primary cell cultures from metastatic melanoma deposits were exposed to three tricyclic drugs, amitriptyline, nortriptyline and clomipramine, at concentrations ranging from 200 to 6.25 µmol/l in the ATP-based tumour chemosensitivity assay. All three drugs showed activity, although nortriptyline was more active than clomipramine or amitriptyline in both cell lines and primary cell cultures, with an IC50 of 9, 27 and 33 µmol/l, respectively.
Substance Class Chemical
Created
by admin
on Thu Jul 06 21:58:24 UTC 2023
Edited
by admin
on Thu Jul 06 21:58:24 UTC 2023
Record UNII
BL03SY4LXB
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
NORTRIPTYLINE
INN   MI   VANDF   WHO-DD  
INN  
Official Name English
NORAMITRIPTYLINE
Common Name English
NSC-757234
Code English
SESAVAL
Common Name English
NORTRIPTYLINE [VANDF]
Common Name English
3-(10,11-DIHYDRO-5H-DIBENZO(A,D)(7)ANNULEN-5-YLIDENE)-N-METHYLPROPAN-1-AMINE
Common Name English
1-PROPANAMINE, 3-(10,11-DIHYDRO-5H-DIBENZO(A,D)CYCLOHEPTEN-5-YLIDENE)-N-METHYL-
Systematic Name English
LUMBECK
Common Name English
AVENTYL
Brand Name English
Nortriptyline [WHO-DD]
Common Name English
nortriptyline [INN]
Common Name English
AMITRIPTYLINE HYDROCHLORIDE IMPURITY C [EP IMPURITY]
Common Name English
NORTRIPTYLINE [MI]
Common Name English
NCI-169453
Code English
NORTRILEN
Brand Name English
DESITRIPTILINA
Common Name English
10,11-DIHYDRO-N-METHYL-5H-DIBENZO(A,D)CYCLOHEPTENE-D(SUP5,.GAMMA.)-PROPYLAMINE
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C94727
Created by admin on Thu Jul 06 21:58:25 UTC 2023 , Edited by admin on Thu Jul 06 21:58:25 UTC 2023
LIVERTOX NBK548526
Created by admin on Thu Jul 06 21:58:25 UTC 2023 , Edited by admin on Thu Jul 06 21:58:25 UTC 2023
WHO-ATC N06AA10
Created by admin on Thu Jul 06 21:58:25 UTC 2023 , Edited by admin on Thu Jul 06 21:58:25 UTC 2023
NDF-RT N0000175752
Created by admin on Thu Jul 06 21:58:25 UTC 2023 , Edited by admin on Thu Jul 06 21:58:25 UTC 2023
WHO-VATC QN06AA10
Created by admin on Thu Jul 06 21:58:25 UTC 2023 , Edited by admin on Thu Jul 06 21:58:25 UTC 2023
Code System Code Type Description
NSC
757234
Created by admin on Thu Jul 06 21:58:25 UTC 2023 , Edited by admin on Thu Jul 06 21:58:25 UTC 2023
PRIMARY
LACTMED
Nortriptyline
Created by admin on Thu Jul 06 21:58:25 UTC 2023 , Edited by admin on Thu Jul 06 21:58:25 UTC 2023
PRIMARY
INN
1328
Created by admin on Thu Jul 06 21:58:25 UTC 2023 , Edited by admin on Thu Jul 06 21:58:25 UTC 2023
PRIMARY
FDA UNII
BL03SY4LXB
Created by admin on Thu Jul 06 21:58:25 UTC 2023 , Edited by admin on Thu Jul 06 21:58:25 UTC 2023
PRIMARY
HSDB
3371
Created by admin on Thu Jul 06 21:58:25 UTC 2023 , Edited by admin on Thu Jul 06 21:58:25 UTC 2023
PRIMARY
EPA CompTox
DTXSID9023384
Created by admin on Thu Jul 06 21:58:25 UTC 2023 , Edited by admin on Thu Jul 06 21:58:25 UTC 2023
PRIMARY
CAS
72-69-5
Created by admin on Thu Jul 06 21:58:25 UTC 2023 , Edited by admin on Thu Jul 06 21:58:25 UTC 2023
PRIMARY
IUPHAR
2404
Created by admin on Thu Jul 06 21:58:25 UTC 2023 , Edited by admin on Thu Jul 06 21:58:25 UTC 2023
PRIMARY
ECHA (EC/EINECS)
200-788-8
Created by admin on Thu Jul 06 21:58:25 UTC 2023 , Edited by admin on Thu Jul 06 21:58:25 UTC 2023
PRIMARY
WIKIPEDIA
NORTRIPTYLINE
Created by admin on Thu Jul 06 21:58:25 UTC 2023 , Edited by admin on Thu Jul 06 21:58:25 UTC 2023
PRIMARY
MERCK INDEX
M8074
Created by admin on Thu Jul 06 21:58:25 UTC 2023 , Edited by admin on Thu Jul 06 21:58:25 UTC 2023
PRIMARY Merck Index
DRUG CENTRAL
1971
Created by admin on Thu Jul 06 21:58:25 UTC 2023 , Edited by admin on Thu Jul 06 21:58:25 UTC 2023
PRIMARY
NCI_THESAURUS
C62060
Created by admin on Thu Jul 06 21:58:25 UTC 2023 , Edited by admin on Thu Jul 06 21:58:25 UTC 2023
PRIMARY
ChEMBL
CHEMBL445
Created by admin on Thu Jul 06 21:58:25 UTC 2023 , Edited by admin on Thu Jul 06 21:58:25 UTC 2023
PRIMARY
RXCUI
7531
Created by admin on Thu Jul 06 21:58:25 UTC 2023 , Edited by admin on Thu Jul 06 21:58:25 UTC 2023
PRIMARY RxNorm
DAILYMED
BL03SY4LXB
Created by admin on Thu Jul 06 21:58:25 UTC 2023 , Edited by admin on Thu Jul 06 21:58:25 UTC 2023
PRIMARY
MESH
D009661
Created by admin on Thu Jul 06 21:58:25 UTC 2023 , Edited by admin on Thu Jul 06 21:58:25 UTC 2023
PRIMARY
EVMPD
SUB09380MIG
Created by admin on Thu Jul 06 21:58:25 UTC 2023 , Edited by admin on Thu Jul 06 21:58:25 UTC 2023
PRIMARY
DRUG BANK
DB00540
Created by admin on Thu Jul 06 21:58:25 UTC 2023 , Edited by admin on Thu Jul 06 21:58:25 UTC 2023
PRIMARY
CHEBI
7640
Created by admin on Thu Jul 06 21:58:25 UTC 2023 , Edited by admin on Thu Jul 06 21:58:25 UTC 2023
PRIMARY
SMS_ID
100000083622
Created by admin on Thu Jul 06 21:58:25 UTC 2023 , Edited by admin on Thu Jul 06 21:58:25 UTC 2023
PRIMARY
PUBCHEM
4543
Created by admin on Thu Jul 06 21:58:25 UTC 2023 , Edited by admin on Thu Jul 06 21:58:25 UTC 2023
PRIMARY
Related Record Type Details
METABOLIC ENZYME -> SUBSTRATE
Metabolizing reaction by CYP2D6: 2-Hydroxylation
TARGET -> INHIBITOR
TRANSPORTER -> SUBSTRATE
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IC50
BINDER->LIGAND
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