NORTRIPTYLINE

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 Search

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

Molecular Formula	C19H21N
Molecular Weight	263.3774
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/018013s063lbl.pdf

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.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Norepinephrine transporter 175 Target ID: CHEMBL222 Sources: https://www.ncbi.nlm.nih.gov/pubmed/10715164	Inhibitor 7728		6.3 nM [Ki]
Alpha-1a adrenergic receptor 64 Target ID: CHEMBL229 Sources: https://www.ncbi.nlm.nih.gov/pubmed/10447960	Antagonist 2575		0.04 nM [IC50]

Conditions

Condition	Modality	Highest Phase	Product
Depression 215 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/018013s063lbl.pdf	Preventing	Approved 8043	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
Plaque psoriasis 15 Sources: https://clinicaltrials.gov/ct2/show/NCT00557739	Primary	Phase II 1101	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
Gastroesophageal reflux disease 45 Sources: https://clinicaltrials.gov/ct2/show/NCT00539240	Primary	Phase III 643	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

C_max

Value	Dose	Co-administered	Analyte	Population
36 nM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/12814461	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 OTHER GOV https://pdf.hres.ca/dpd_pm/00001266.PDF	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

Value	Dose	Co-administered	Analyte	Population
1591 nM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/12814461	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 OTHER GOV https://pdf.hres.ca/dpd_pm/00001266.PDF	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

T_1/2

Value	Dose	Co-administered	Analyte	Population
29.3 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/12814461	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 OTHER GOV https://pdf.hres.ca/dpd_pm/00001266.PDF	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

F_unbound

Value	Dose	Co-administered	Analyte	Population
8.35% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7094510			NORTRIPTYLINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1601		substrate 1118	inhibitor 1475

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP2E1 790	CYP2C19 910 CYP1A2 972

Drug as perpetrator

Target	Modality	Activity	Metabolite	Clinical evidence
CYP2E1 871	inhibitor 3045 Sources: https://pubmed.ncbi.nlm.nih.gov/9574817/ Page: 7.0	yes [Ki 450 uM]

Drug as victim

Target	Modality	Activity	Clinical evidence
CYP2D6 1118	substrate 3113 Sources: https://dmd.aspetjournals.org/content/25/6/740; https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/018012s031lbl.pdf#page=18	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 Sources: https://dmd.aspetjournals.org/content/25/6/740; https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/018012s031lbl.pdf#page=18
CYP1A2 972	substrate 3113 Sources: https://dmd.aspetjournals.org/content/25/6/740	minor
CYP2C19 910	substrate 3113 Sources: https://dmd.aspetjournals.org/content/25/6/740	minor
CYP3A4 1601	substrate 3113 Sources: https://pubmed.ncbi.nlm.nih.gov/10354960/	yes

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1507	inhibitor 1489 Sources: https://pubmed.ncbi.nlm.nih.gov/21262863/

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:7640	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:7640
ChemicalBook	CB1317147	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB1317147
ZINC	ZINC000001530741	http://zinc15.docking.org/substances/ZINC000001530741

PubMed

Title	Date	PubMed
Amitriptyline and heart block.	1967 Jul 29	6028741
Correlation of subjective side effects with plasma concentrations of nortriptyline.	1970 Oct 3	5470429
Tricyclic antidepressants and monoamine oxidase inhibitors.	1971 Jun	5578096
Ophthalmological effects of nortriptyline--relationship to plasma level.	1972	4566251
Ototoxic reaction associated with use of nortriptyline hydrochloride: case report.	1972 Jun	5026029
Urinary retention in a neonate secondary to maternal ingestion of nortriptyline.	1972 Sep	5049831
Electrocardiographic changes and cardiac arrhythmias in patients receiving psychotropic drugs.	1976 Feb	2004
[Double blind clinical study of mianserin and nortriptyline (author's transl)].	1978 Sep-Oct	375687
Hoarseness and aphonia as a side effect of tricyclic antidepressants.	1979 Dec	507219
Cardiovascular side effects of long-term therapy with tricyclic antidepressants in the aged.	1979 May	429744
Hoarseness and tricyclic antidepressants.	1980 May	7369424
Comparison of imipramine- and nortriptyline-induced orthostatic hypotension: a meaningful difference.	1981 Sep	6277997
Marked sinus tachycardia resulting from the synergistic effects of marijuana and nortriptyline.	1983 May	6303138
Psychosis after discontinuation of nortriptyline.	1984 Apr	6707238
Comparative efficacy and safety of MAOIs versus TCAs in treating depression in the elderly.	1986 Oct	3756264
Occurrence of myoclonus in patients treated with cyclic antidepressants.	1987 Mar	3827519
Treatment-emergent depression with antidepressants in panic disorder.	1989 May-Jun	2731426
Myoclonus caused by a tricyclic antidepressant.	1990 Apr	2181694
Low dose tricyclic tachycardia.	1991 Jan	1810269
Tricyclics and heart failure.	1991 Nov	1928479
Downregulation of serotonin receptor subtypes by nortriptyline and adinazolam in major depressive disorder: neuroendocrine and platelet markers.	1993	8131152
High initial nortriptyline doses in the treatment of depression.	1993 Feb	8444823
Midodrine for TCA-induced orthostatic hypotension.	1993 Nov	7507712
Sleep in bereavement-related depression during and after pharmacotherapy with nortriptyline.	1994 Apr-Jun	8204191
Recurrent hypotension immediately after seizures in nortriptyline overdose.	1994 Jul	8031432
The cardiovascular effects of bupropion and nortriptyline in depressed outpatients.	1994 Jun	7804386
Nortriptyline-induced fulminant hepatic failure.	1995 Jan	7884180
Mixed mania: apparent induction by a tricyclic antidepressant in five consecutively treated patients with bipolar depression.	1995 Jan 1	7893862
Depression following smoking cessation in women.	1996	8743774
Nortriptyline-induced hepatic failure.	1996 Feb	8848811
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	15844547
The adsorption mechanism of nortryptiline on C18-bonded Discovery.	2005 Nov 18	16275280
[A case of Brugada syndrome with convulsive seizure during antidepressant administration: relation of antidepressant agents and arrhythmia leading to sudden death].	2006	17089931
Gabapentin versus nortriptyline in post-herpetic neuralgia patients: a randomized, double-blind clinical trial--the GONIP Trial.	2006 Aug	16961166
[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	16856516
Photoinduced chemiluminescence of pharmaceuticals.	2006 May 3	16413738
Monoamine transporter gene polymorphisms and antidepressant response in koreans with late-life depression.	2006 Oct 4	17018806
Comparative metabolic capabilities and inhibitory profiles of CYP2D6.1, CYP2D6.10, and CYP2D6.17.	2007 Aug	17470523
In silico prediction of pregnane X receptor activators by machine learning approaches.	2007 Jan	17003167
Tobacco smoking cessation management: integrating varenicline in current practice.	2008	19066000
Nortriptyline protects mitochondria and reduces cerebral ischemia/hypoxia injury.	2008 Feb	18174477
Possession states precipitated by nortriptyline.	2008 May	18499931
Bioactivation of the tricyclic antidepressant amitriptyline and its metabolite nortriptyline to arene oxide intermediates in human liver microsomes and recombinant P450s.	2008 May 9	18359012
Community-based randomised controlled trial evaluating falls and osteoporosis risk management strategies.	2008 Nov 4	18983670
Trifluoperazine: a rynodine receptor agonist.	2009 Aug	19277699
Synergistic drug-cytokine induction of hepatocellular death as an in vitro approach for the study of inflammation-associated idiosyncratic drug hepatotoxicity.	2009 Jun 15	19362101
A new strategy for antidepressant prescription.	2010	21151361
Development of a list of potentially inappropriate drugs for the korean elderly using the delphi method.	2010 Dec	21818443
Profiling of a prescription drug library for potential renal drug-drug interactions mediated by the organic cation transporter 2.	2011 Jul 14	21599003
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	22700542

Patents

Sample Use Guides

In Vivo Use Guide

25mg PO q6-8hr. No more than 150 mg/day

Route of Administration: Oral

In Vitro Use Guide

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 `Fri Jun 25 21:56:48 UTC 2021` Edited by `admin` on `Fri Jun 25 21:56:48 UTC 2021`
Record UNII	BL03SY4LXB
Record Status	`Validated (UNII)`
Record Version

Download

Name

Type

Language

NORTRIPTYLINE

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