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

Details

Stereochemistry ACHIRAL
Molecular Formula C19H21N.ClH
Molecular Weight 299.838
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of NORTRIPTYLINE HYDROCHLORIDE

SMILES

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

InChI

InChIKey=SHAYBENGXDALFF-UHFFFAOYSA-N
InChI=1S/C19H21N.ClH/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;1H

HIDE SMILES / InChI

Molecular Formula ClH
Molecular Weight 36.461
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

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
Tricyclic antidepressants and monoamine oxidase inhibitors.
1971 Jun
Ototoxic reaction associated with use of nortriptyline hydrochloride: case report.
1972 Jun
Electrocardiographic changes and cardiac arrhythmias in patients receiving psychotropic drugs.
1976 Feb
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
Use of yohimbine to counteract nortriptyline-induced orthostatic hypotension.
1989 Feb
Simulated home treatment of depression with nortriptyline.
1991
Low dose tricyclic tachycardia.
1991 Jan
Tricyclics and heart failure.
1991 Nov
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
Sleep in bereavement-related depression during and after pharmacotherapy with nortriptyline.
1994 Apr-Jun
Depression following smoking cessation in women.
1996
Nortriptyline-induced hepatic failure.
1996 Feb
The promises and pitfalls of reboxetine.
2003 Winter
Drug analysis in blowfly larvae and in human tissues: a comparative study.
2004 Aug
Mechanism-based inactivation of human cytochrome P4502C8 by drugs in vitro.
2004 Dec
Spasmodic dysphonia, a rare form of tardive dystonia, induced by low-dose risperidone?
2004 Mar
Inhibition of G protein-activated inwardly rectifying K+ channels by various antidepressant drugs.
2004 Oct
Efficacy of antidepressants in substance use disorders with and without comorbid depression. A systematic review and meta-analysis.
2005 Apr 4
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
The adsorption mechanism of nortryptiline on C18-bonded Discovery.
2005 Nov 18
[A case of Brugada syndrome with convulsive seizure during antidepressant administration: relation of antidepressant agents and arrhythmia leading to sudden death].
2006
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
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
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
Development of a list of potentially inappropriate drugs for the korean elderly using the delphi method.
2010 Dec
An overview of Indian research in anxiety disorders.
2010 Jan
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.
Substance Class Chemical
Created
by admin
on Sat Dec 16 05:10:51 GMT 2023
Edited
by admin
on Sat Dec 16 05:10:51 GMT 2023
Record UNII
00FN6IH15D
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
NORTRIPTYLINE HYDROCHLORIDE
EP   HSDB   MART.   MI   ORANGE BOOK   USAN   USP   USP-RS   VANDF   WHO-DD  
USAN  
Official Name English
NORTRIPTYLINE HYDROCHLORIDE [USP MONOGRAPH]
Common Name English
38489
Code English
Nortriptyline hydrochloride [WHO-DD]
Common Name English
NORTRIPTYLINE HYDROCHLORIDE [JAN]
Common Name English
PAMELOR
Brand Name English
NORTRIPTYLINE HYDROCHLORIDE [USAN]
Common Name English
NORTRIPTYLINE HCL
Common Name English
10,11-DIHYDRO-N-METHYL-5H-DIBENZO(A,D)CYCLOHEPTENE-D(SUP5,.GAMMA.)-PROPYLAMINE HYDROCHLORIDE
Common Name English
NORTRIPTYLINE HYDROCHLORIDE [HSDB]
Common Name English
NORTRIPTYLINE HYDROCHLORIDE [EP MONOGRAPH]
Common Name English
1-PROPANAMINE, 3-(10,11-DIHYDRO-5H-DIBENZO(A,D)CYCLOHEPTEN-5-YLIDENE)-N-METHYL-, HYDROCHLORIDE
Systematic Name English
NSC-169453
Code English
NORTRIPTYLINE HYDROCHLORIDE [MART.]
Common Name English
NORTRIPTYLINE HYDROCHLORIDE [VANDF]
Common Name English
AVENTYL HYDROCHLORIDE
Brand Name English
NORTRIPTYLINE HYDROCHLORIDE [ORANGE BOOK]
Common Name English
NORTRIPTYLINE HYDROCHLORIDE [USP-RS]
Common Name English
NORTRIPTYLINE HYDROCHLORIDE [MI]
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C94727
Created by admin on Sat Dec 16 05:10:51 GMT 2023 , Edited by admin on Sat Dec 16 05:10:51 GMT 2023
Code System Code Type Description
NSC
169453
Created by admin on Sat Dec 16 05:10:51 GMT 2023 , Edited by admin on Sat Dec 16 05:10:51 GMT 2023
PRIMARY
NCI_THESAURUS
C704
Created by admin on Sat Dec 16 05:10:51 GMT 2023 , Edited by admin on Sat Dec 16 05:10:51 GMT 2023
PRIMARY
ChEMBL
CHEMBL445
Created by admin on Sat Dec 16 05:10:51 GMT 2023 , Edited by admin on Sat Dec 16 05:10:51 GMT 2023
PRIMARY
RS_ITEM_NUM
1474005
Created by admin on Sat Dec 16 05:10:51 GMT 2023 , Edited by admin on Sat Dec 16 05:10:51 GMT 2023
PRIMARY
EPA CompTox
DTXSID2045109
Created by admin on Sat Dec 16 05:10:51 GMT 2023 , Edited by admin on Sat Dec 16 05:10:51 GMT 2023
PRIMARY
MERCK INDEX
m8074
Created by admin on Sat Dec 16 05:10:51 GMT 2023 , Edited by admin on Sat Dec 16 05:10:51 GMT 2023
PRIMARY Merck Index
DRUG BANK
DBSALT000641
Created by admin on Sat Dec 16 05:10:51 GMT 2023 , Edited by admin on Sat Dec 16 05:10:51 GMT 2023
PRIMARY
ECHA (EC/EINECS)
212-973-0
Created by admin on Sat Dec 16 05:10:51 GMT 2023 , Edited by admin on Sat Dec 16 05:10:51 GMT 2023
PRIMARY
DAILYMED
00FN6IH15D
Created by admin on Sat Dec 16 05:10:51 GMT 2023 , Edited by admin on Sat Dec 16 05:10:51 GMT 2023
PRIMARY
PUBCHEM
13468
Created by admin on Sat Dec 16 05:10:51 GMT 2023 , Edited by admin on Sat Dec 16 05:10:51 GMT 2023
PRIMARY
CAS
894-71-3
Created by admin on Sat Dec 16 05:10:51 GMT 2023 , Edited by admin on Sat Dec 16 05:10:51 GMT 2023
PRIMARY
FDA UNII
00FN6IH15D
Created by admin on Sat Dec 16 05:10:51 GMT 2023 , Edited by admin on Sat Dec 16 05:10:51 GMT 2023
PRIMARY
SMS_ID
100000085743
Created by admin on Sat Dec 16 05:10:51 GMT 2023 , Edited by admin on Sat Dec 16 05:10:51 GMT 2023
PRIMARY
RXCUI
203130
Created by admin on Sat Dec 16 05:10:51 GMT 2023 , Edited by admin on Sat Dec 16 05:10:51 GMT 2023
PRIMARY RxNorm
EVMPD
SUB03464MIG
Created by admin on Sat Dec 16 05:10:51 GMT 2023 , Edited by admin on Sat Dec 16 05:10:51 GMT 2023
PRIMARY
CAS
1001637-77-9
Created by admin on Sat Dec 16 05:10:51 GMT 2023 , Edited by admin on Sat Dec 16 05:10:51 GMT 2023
NO STRUCTURE GIVEN
Related Record Type Details
BASIS OF STRENGTH->SUBSTANCE
ASSAY (TITRATION)
EP
BASIS OF STRENGTH->SUBSTANCE
ASSAY (TITRATION)
USP
PARENT -> SALT/SOLVATE
Related Record Type Details
IMPURITY -> PARENT
For the calculation of contents, multiply the peak areas by 1.7
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
IMPURITY -> PARENT
UNSPECIFIED
EP
IMPURITY -> PARENT
UNSPECIFIED
EP
IMPURITY -> PARENT
UNSPECIFIED
EP
IMPURITY -> PARENT
UNSPECIFIED
EP
IMPURITY -> PARENT
UNSPECIFIED
EP
IMPURITY -> PARENT
UNSPECIFIED
EP
IMPURITY -> PARENT
UNSPECIFIED
EP
Related Record Type Details
ACTIVE MOIETY