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Details

Stereochemistry ACHIRAL
Molecular Formula C19H21N
Molecular Weight 263.3774
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of NORTRIPTYLINE

SMILES

CNCCC=C1c2ccccc2CCc3ccccc31

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
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
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
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
Slow tricyclic antidepressant metabolism, polypharmacy, and cardiac arrest.
1980 Jan
Hoarseness and tricyclic antidepressants.
1980 May
Atrial flutter with amoxapine: a case report.
1981 Nov
Comparison of imipramine- and nortriptyline-induced orthostatic hypotension: a meaningful difference.
1981 Sep
The clinical efficacy and side-effects of mianserin and nortriptyline in depressed out-patients: a double-blind randomized trial.
1982
Marked sinus tachycardia resulting from the synergistic effects of marijuana and nortriptyline.
1983 May
Psychosis after discontinuation of nortriptyline.
1984 Apr
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
The effects of mood changes and antidepressants on the cognitive capacity of elderly depressed patients.
1989 Fall
Tryptophan antagonism of stimulant-induced tics.
1989 Feb
Use of yohimbine to counteract nortriptyline-induced orthostatic hypotension.
1989 Feb
Myoclonus caused by a tricyclic antidepressant.
1990 Apr
Simulated home treatment of depression with nortriptyline.
1991
Tricyclics and heart failure.
1991 Nov
Left bundle branch block developing in a patient with sub-therapeutic nortriptyline levels: a case report.
1991 Oct
Downregulation of serotonin receptor subtypes by nortriptyline and adinazolam in major depressive disorder: neuroendocrine and platelet markers.
1993
High initial nortriptyline doses in the treatment of depression.
1993 Feb
Midodrine for TCA-induced orthostatic hypotension.
1993 Nov
Sleep in bereavement-related depression during and after pharmacotherapy with nortriptyline.
1994 Apr-Jun
Recurrent hypotension immediately after seizures in nortriptyline overdose.
1994 Jul
The cardiovascular effects of bupropion and nortriptyline in depressed outpatients.
1994 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
Tobacco smoking cessation management: integrating varenicline in current practice.
2008
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
Citalopram associated with complex visual hallucination: a case report.
2009 Apr 30
Trifluoperazine: a rynodine receptor agonist.
2009 Aug
Synergistic drug-cytokine induction of hepatocellular death as an in vitro approach for the study of inflammation-associated idiosyncratic drug hepatotoxicity.
2009 Jun 15
Adverse reactions to antidepressants.
2009 Sep
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
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
Genetic variants in the serotonin transporter influence the efficacy of bupropion and nortriptyline in smoking cessation.
2012 Jan
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.
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
AMITRIPTYLINE HYDROCHLORIDE IMPURITY C [EP]
Common Name English
NORTRIPTYLINE [INN]
Common Name English
NORTRIPTYLINE [MI]
Common Name English
NORTRIPTYLINE [WHO-DD]
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 Fri Jun 25 21:56:48 UTC 2021 , Edited by admin on Fri Jun 25 21:56:48 UTC 2021
LIVERTOX 700
Created by admin on Fri Jun 25 21:56:48 UTC 2021 , Edited by admin on Fri Jun 25 21:56:48 UTC 2021
WHO-ATC N06AA10
Created by admin on Fri Jun 25 21:56:48 UTC 2021 , Edited by admin on Fri Jun 25 21:56:48 UTC 2021
NDF-RT N0000175752
Created by admin on Fri Jun 25 21:56:48 UTC 2021 , Edited by admin on Fri Jun 25 21:56:48 UTC 2021
WHO-VATC QN06AA10
Created by admin on Fri Jun 25 21:56:48 UTC 2021 , Edited by admin on Fri Jun 25 21:56:48 UTC 2021
Code System Code Type Description
LACTMED
Nortriptyline
Created by admin on Fri Jun 25 21:56:48 UTC 2021 , Edited by admin on Fri Jun 25 21:56:48 UTC 2021
PRIMARY
INN
1328
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PRIMARY
FDA UNII
BL03SY4LXB
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PRIMARY
HSDB
3371
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PRIMARY
EPA CompTox
72-69-5
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PRIMARY
CAS
72-69-5
Created by admin on Fri Jun 25 21:56:48 UTC 2021 , Edited by admin on Fri Jun 25 21:56:48 UTC 2021
PRIMARY
IUPHAR
2404
Created by admin on Fri Jun 25 21:56:48 UTC 2021 , Edited by admin on Fri Jun 25 21:56:48 UTC 2021
PRIMARY
ECHA (EC/EINECS)
200-788-8
Created by admin on Fri Jun 25 21:56:48 UTC 2021 , Edited by admin on Fri Jun 25 21:56:48 UTC 2021
PRIMARY
WIKIPEDIA
NORTRIPTYLINE
Created by admin on Fri Jun 25 21:56:48 UTC 2021 , Edited by admin on Fri Jun 25 21:56:48 UTC 2021
PRIMARY
MERCK INDEX
M8074
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PRIMARY Merck Index
DRUG CENTRAL
1971
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PRIMARY
NCI_THESAURUS
C62060
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PRIMARY
ChEMBL
CHEMBL445
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PRIMARY
RXCUI
7531
Created by admin on Fri Jun 25 21:56:48 UTC 2021 , Edited by admin on Fri Jun 25 21:56:48 UTC 2021
PRIMARY RxNorm
MESH
D009661
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PRIMARY
EVMPD
SUB09380MIG
Created by admin on Fri Jun 25 21:56:48 UTC 2021 , Edited by admin on Fri Jun 25 21:56:48 UTC 2021
PRIMARY
DRUG BANK
DB00540
Created by admin on Fri Jun 25 21:56:48 UTC 2021 , Edited by admin on Fri Jun 25 21:56:48 UTC 2021
PRIMARY
PUBCHEM
4543
Created by admin on Fri Jun 25 21:56:48 UTC 2021 , Edited by admin on Fri Jun 25 21:56:48 UTC 2021
PRIMARY