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

-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
Tricyclic antidepressants and monoamine oxidase inhibitors.
1971 Jun
Electrocardiographic changes and cardiac arrhythmias in patients receiving psychotropic drugs.
1976 Feb
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
Occurrence of myoclonus in patients treated with cyclic antidepressants.
1987 Mar
The effects of mood changes and antidepressants on the cognitive capacity of elderly depressed patients.
1989 Fall
Use of yohimbine to counteract nortriptyline-induced orthostatic hypotension.
1989 Feb
Naproxen reversal of nortriptyline-induced orthostatic hypotension.
1989 Sep
Myoclonus caused by a tricyclic antidepressant.
1990 Apr
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
[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
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
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
Synergistic drug-cytokine induction of hepatocellular death as an in vitro approach for the study of inflammation-associated idiosyncratic drug hepatotoxicity.
2009 Jun 15
A new strategy for antidepressant prescription.
2010
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
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
Identification of human Ether-à-go-go related gene modulators by three screening platforms in an academic drug-discovery setting.
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
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 10:57:58 UTC 2023
Edited
by admin
on Thu Jul 06 10:57:58 UTC 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 Thu Jul 06 10:57:58 UTC 2023 , Edited by admin on Thu Jul 06 10:57:58 UTC 2023
Code System Code Type Description
NSC
169453
Created by admin on Thu Jul 06 10:57:58 UTC 2023 , Edited by admin on Thu Jul 06 10:57:58 UTC 2023
PRIMARY
NCI_THESAURUS
C704
Created by admin on Thu Jul 06 10:57:58 UTC 2023 , Edited by admin on Thu Jul 06 10:57:58 UTC 2023
PRIMARY
ChEMBL
CHEMBL445
Created by admin on Thu Jul 06 10:57:58 UTC 2023 , Edited by admin on Thu Jul 06 10:57:58 UTC 2023
PRIMARY
RS_ITEM_NUM
1474005
Created by admin on Thu Jul 06 10:57:58 UTC 2023 , Edited by admin on Thu Jul 06 10:57:58 UTC 2023
PRIMARY
EPA CompTox
DTXSID2045109
Created by admin on Thu Jul 06 10:57:58 UTC 2023 , Edited by admin on Thu Jul 06 10:57:58 UTC 2023
PRIMARY
MERCK INDEX
M8074
Created by admin on Thu Jul 06 10:57:58 UTC 2023 , Edited by admin on Thu Jul 06 10:57:58 UTC 2023
PRIMARY Merck Index
DRUG BANK
DBSALT000641
Created by admin on Thu Jul 06 10:57:58 UTC 2023 , Edited by admin on Thu Jul 06 10:57:58 UTC 2023
PRIMARY
ECHA (EC/EINECS)
212-973-0
Created by admin on Thu Jul 06 10:57:58 UTC 2023 , Edited by admin on Thu Jul 06 10:57:58 UTC 2023
PRIMARY
DAILYMED
00FN6IH15D
Created by admin on Thu Jul 06 10:57:58 UTC 2023 , Edited by admin on Thu Jul 06 10:57:58 UTC 2023
PRIMARY
PUBCHEM
13468
Created by admin on Thu Jul 06 10:57:58 UTC 2023 , Edited by admin on Thu Jul 06 10:57:58 UTC 2023
PRIMARY
CAS
894-71-3
Created by admin on Thu Jul 06 10:57:58 UTC 2023 , Edited by admin on Thu Jul 06 10:57:58 UTC 2023
PRIMARY
FDA UNII
00FN6IH15D
Created by admin on Thu Jul 06 10:57:58 UTC 2023 , Edited by admin on Thu Jul 06 10:57:58 UTC 2023
PRIMARY
SMS_ID
100000085743
Created by admin on Thu Jul 06 10:57:58 UTC 2023 , Edited by admin on Thu Jul 06 10:57:58 UTC 2023
PRIMARY
RXCUI
203130
Created by admin on Thu Jul 06 10:57:58 UTC 2023 , Edited by admin on Thu Jul 06 10:57:58 UTC 2023
PRIMARY RxNorm
EVMPD
SUB03464MIG
Created by admin on Thu Jul 06 10:57:58 UTC 2023 , Edited by admin on Thu Jul 06 10:57:58 UTC 2023
PRIMARY
CAS
1001637-77-9
Created by admin on Thu Jul 06 10:57:58 UTC 2023 , Edited by admin on Thu Jul 06 10:57:58 UTC 2023
NO STRUCTURE GIVEN
Related Record Type Details
BASIS OF STRENGTH->SUBSTANCE
ASSAY (TITRATION)
EP
BASIS OF STRENGTH->SUBSTANCE
ASSAY (TITRATION)
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PARENT -> SALT/SOLVATE
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For the calculation of contents, multiply the peak areas by 1.7
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