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

1964
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

1964
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

1964
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
Ophthalmological effects of nortriptyline--relationship to plasma level.
1972
Ototoxic reaction associated with use of nortriptyline hydrochloride: case report.
1972 Jun
Urinary retention in a neonate secondary to maternal ingestion of nortriptyline.
1972 Sep
[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
Atrial flutter with amoxapine: a case report.
1981 Nov
The antiarrhythmic effect of nortriptyline in cardiac patients with ventricular premature depolarizations.
1986 Jun
Comparative efficacy and safety of MAOIs versus TCAs in treating depression in the elderly.
1986 Oct
A placebo-controlled comparison of the effect of nortriptyline and phenelzine on orthostatic hypotension in elderly depressed patients.
1987 Dec
Occurrence of myoclonus in patients treated with cyclic antidepressants.
1987 Mar
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
Tricyclics and heart failure.
1991 Nov
Cognitive decline with nortriptyline use in a patient with dementia of the Alzheimer's type.
1992 Jan
Midodrine for TCA-induced orthostatic hypotension.
1993 Nov
The cardiovascular effects of bupropion and nortriptyline in depressed outpatients.
1994 Jun
Mixed mania: apparent induction by a tricyclic antidepressant in five consecutively treated patients with bipolar depression.
1995 Jan 1
Extrapyramidal symptoms associated with the adjunct of nortriptyline to a venlafaxine-valproic acid combination.
1999 May
Effects of nortriptyline and paroxetine on QT variability in patients with panic disorder.
2000
Inhibition of HIV replication by neuroleptic agents and their potential use in HIV infected patients with AIDS related dementia.
2000 Apr
2-Substituted tryptamines: agents with selectivity for 5-HT(6) serotonin receptors.
2000 Mar 9
Sex-related differences in nortriptyline-induced side-effects among depressed patients.
2001 Jul
Treatment options for depression and psychosis in Parkinson's disease.
2001 Sep
Phase III evaluation of nortriptyline for alleviation of symptoms of cis-platinum-induced peripheral neuropathy.
2002 Jul
Risk factors for falls during treatment of late-life depression.
2002 Oct
Mechanism-based inactivation of human cytochrome P4502C8 by drugs in vitro.
2004 Dec
Interactions of cyclobenzaprine and tricyclic antidepressants.
2005 Jan
Gabapentin versus nortriptyline in post-herpetic neuralgia patients: a randomized, double-blind clinical trial--the GONIP Trial.
2006 Aug
[Trazodone for the treatment of behavioral and psychological symptoms of dementia (BPSD) in Alzheimer's disease: a retrospective study focused on the aggression and negativism in caregiving situations].
2006 Jun
Photoinduced chemiluminescence of pharmaceuticals.
2006 May 3
Monoamine transporter gene polymorphisms and antidepressant response in koreans with late-life depression.
2006 Oct 4
Nortriptyline delays disease onset in models of chronic neurodegeneration.
2007 Aug
Comparative metabolic capabilities and inhibitory profiles of CYP2D6.1, CYP2D6.10, and CYP2D6.17.
2007 Aug
Inhibition of astroglial inwardly rectifying Kir4.1 channels by a tricyclic antidepressant, nortriptyline.
2007 Feb
In silico prediction of pregnane X receptor activators by machine learning approaches.
2007 Jan
Tobacco smoking cessation management: integrating varenicline in current practice.
2008
Community-based randomised controlled trial evaluating falls and osteoporosis risk management strategies.
2008 Nov 4
Spontaneous hypothermia on intensive care unit admission is a predictor of unfavorable neurological outcome in patients after resuscitation: an observational cohort study.
2010
3D-QSAR design of new escitalopram derivatives for the treatment of major depressive disorders.
2010 Apr-Jun
Identification of human Ether-à-go-go related gene modulators by three screening platforms in an academic drug-discovery setting.
2010 Dec
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
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 Sat Dec 16 16:29:26 GMT 2023
Edited
by admin
on Sat Dec 16 16:29:26 GMT 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 Sat Dec 16 16:29:27 GMT 2023 , Edited by admin on Sat Dec 16 16:29:27 GMT 2023
LIVERTOX NBK548526
Created by admin on Sat Dec 16 16:29:27 GMT 2023 , Edited by admin on Sat Dec 16 16:29:27 GMT 2023
WHO-ATC N06AA10
Created by admin on Sat Dec 16 16:29:27 GMT 2023 , Edited by admin on Sat Dec 16 16:29:27 GMT 2023
NDF-RT N0000175752
Created by admin on Sat Dec 16 16:29:27 GMT 2023 , Edited by admin on Sat Dec 16 16:29:27 GMT 2023
WHO-VATC QN06AA10
Created by admin on Sat Dec 16 16:29:27 GMT 2023 , Edited by admin on Sat Dec 16 16:29:27 GMT 2023
Code System Code Type Description
NSC
757234
Created by admin on Sat Dec 16 16:29:27 GMT 2023 , Edited by admin on Sat Dec 16 16:29:27 GMT 2023
PRIMARY
LACTMED
Nortriptyline
Created by admin on Sat Dec 16 16:29:27 GMT 2023 , Edited by admin on Sat Dec 16 16:29:27 GMT 2023
PRIMARY
INN
1328
Created by admin on Sat Dec 16 16:29:27 GMT 2023 , Edited by admin on Sat Dec 16 16:29:27 GMT 2023
PRIMARY
FDA UNII
BL03SY4LXB
Created by admin on Sat Dec 16 16:29:27 GMT 2023 , Edited by admin on Sat Dec 16 16:29:27 GMT 2023
PRIMARY
HSDB
3371
Created by admin on Sat Dec 16 16:29:27 GMT 2023 , Edited by admin on Sat Dec 16 16:29:27 GMT 2023
PRIMARY
EPA CompTox
DTXSID9023384
Created by admin on Sat Dec 16 16:29:27 GMT 2023 , Edited by admin on Sat Dec 16 16:29:27 GMT 2023
PRIMARY
CAS
72-69-5
Created by admin on Sat Dec 16 16:29:27 GMT 2023 , Edited by admin on Sat Dec 16 16:29:27 GMT 2023
PRIMARY
IUPHAR
2404
Created by admin on Sat Dec 16 16:29:27 GMT 2023 , Edited by admin on Sat Dec 16 16:29:27 GMT 2023
PRIMARY
ECHA (EC/EINECS)
200-788-8
Created by admin on Sat Dec 16 16:29:27 GMT 2023 , Edited by admin on Sat Dec 16 16:29:27 GMT 2023
PRIMARY
WIKIPEDIA
NORTRIPTYLINE
Created by admin on Sat Dec 16 16:29:27 GMT 2023 , Edited by admin on Sat Dec 16 16:29:27 GMT 2023
PRIMARY
MERCK INDEX
m8074
Created by admin on Sat Dec 16 16:29:27 GMT 2023 , Edited by admin on Sat Dec 16 16:29:27 GMT 2023
PRIMARY Merck Index
DRUG CENTRAL
1971
Created by admin on Sat Dec 16 16:29:27 GMT 2023 , Edited by admin on Sat Dec 16 16:29:27 GMT 2023
PRIMARY
NCI_THESAURUS
C62060
Created by admin on Sat Dec 16 16:29:27 GMT 2023 , Edited by admin on Sat Dec 16 16:29:27 GMT 2023
PRIMARY
ChEMBL
CHEMBL445
Created by admin on Sat Dec 16 16:29:27 GMT 2023 , Edited by admin on Sat Dec 16 16:29:27 GMT 2023
PRIMARY
RXCUI
7531
Created by admin on Sat Dec 16 16:29:27 GMT 2023 , Edited by admin on Sat Dec 16 16:29:27 GMT 2023
PRIMARY RxNorm
DAILYMED
BL03SY4LXB
Created by admin on Sat Dec 16 16:29:27 GMT 2023 , Edited by admin on Sat Dec 16 16:29:27 GMT 2023
PRIMARY
MESH
D009661
Created by admin on Sat Dec 16 16:29:27 GMT 2023 , Edited by admin on Sat Dec 16 16:29:27 GMT 2023
PRIMARY
EVMPD
SUB09380MIG
Created by admin on Sat Dec 16 16:29:27 GMT 2023 , Edited by admin on Sat Dec 16 16:29:27 GMT 2023
PRIMARY
DRUG BANK
DB00540
Created by admin on Sat Dec 16 16:29:27 GMT 2023 , Edited by admin on Sat Dec 16 16:29:27 GMT 2023
PRIMARY
CHEBI
7640
Created by admin on Sat Dec 16 16:29:27 GMT 2023 , Edited by admin on Sat Dec 16 16:29:27 GMT 2023
PRIMARY
SMS_ID
100000083622
Created by admin on Sat Dec 16 16:29:27 GMT 2023 , Edited by admin on Sat Dec 16 16:29:27 GMT 2023
PRIMARY
PUBCHEM
4543
Created by admin on Sat Dec 16 16:29:27 GMT 2023 , Edited by admin on Sat Dec 16 16:29:27 GMT 2023
PRIMARY
Related Record Type Details
METABOLIC ENZYME -> SUBSTRATE
Metabolizing reaction by CYP2D6: 2-Hydroxylation
TARGET -> INHIBITOR
METABOLIC ENZYME -> INHIBITOR
IC50
BINDER->LIGAND
TRANSPORTER -> SUBSTRATE
METABOLIC ENZYME -> SUBSTRATE
Pharmacological action: Tricyclic antidepressant drug (TCA)
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