NORTRIPTYLINE HYDROCHLORIDE

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

Structure Search

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

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 191 Target ID: CHEMBL222 Sources: https://www.ncbi.nlm.nih.gov/pubmed/10715164	Inhibitor 8297		6.3 nM [Ki]
Alpha-1a adrenergic receptor 66 Target ID: CHEMBL229 Sources: https://www.ncbi.nlm.nih.gov/pubmed/10447960	Antagonist 2778		0.04 nM [IC50]

Conditions

Condition	Modality	Highest Phase	Product
Depression 235 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/018013s063lbl.pdf	Preventing	Approved 8429	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
Plaque psoriasis 16 Sources: https://clinicaltrials.gov/ct2/show/NCT00557739	Primary	Phase II 1132	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
Gastroesophageal reflux disease 59 Sources: https://clinicaltrials.gov/ct2/show/NCT00539240	Primary	Phase III 656	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

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 1737		substrate 1217	inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP2E1 882	CYP2C19 991 CYP1A2 1054

Drug as perpetrator

Target	Modality	Activity	Metabolite	Clinical evidence
CYP2E1 970	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/9574817/ Page: 7.0	yes [Ki 450 uM]

Drug as victim

Target	Modality	Activity	Clinical evidence
CYP2D6 1217	substrate 3367 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 1054	substrate 3367 Sources: https://dmd.aspetjournals.org/content/25/6/740	minor
CYP2C19 991	substrate 3367 Sources: https://dmd.aspetjournals.org/content/25/6/740	minor
CYP3A4 1737	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/10354960/	yes

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1647	inhibitor 1626 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
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
Slow tricyclic antidepressant metabolism, polypharmacy, and cardiac arrest.	1980 Jan	7352543
Psychosis after discontinuation of nortriptyline.	1984 Apr	6707238
Tryptophan antagonism of stimulant-induced tics.	1989 Feb	2708560
Use of yohimbine to counteract nortriptyline-induced orthostatic hypotension.	1989 Feb	2708559
Left bundle branch block developing in a patient with sub-therapeutic nortriptyline levels: a case report.	1991 Oct	1918772
Cognitive decline with nortriptyline use in a patient with dementia of the Alzheimer's type.	1992 Jan	1734612
Midodrine for TCA-induced orthostatic hypotension.	1993 Nov	7507712
The cardiovascular effects of bupropion and nortriptyline in depressed outpatients.	1994 Jun	7804386
Nortriptyline-induced fulminant hepatic failure.	1995 Jan	7884180
Inhibition of HIV replication by neuroleptic agents and their potential use in HIV infected patients with AIDS related dementia.	2000 Apr	10773489
Evaluation of platelet activation in depressed patients with ischemic heart disease after paroxetine or nortriptyline treatment.	2000 Apr	10770450
Treatment options for depression and psychosis in Parkinson's disease.	2001 Sep	11697683
A common P-glycoprotein polymorphism is associated with nortriptyline-induced postural hypotension in patients treated for major depression.	2002	12082591
Nortriptyline effective for smoking cessation.	2002 Dec	12540319
Interactions of cyclobenzaprine and tricyclic antidepressants.	2005 Jan	15669899
[A case of Brugada syndrome with convulsive seizure during antidepressant administration: relation of antidepressant agents and arrhythmia leading to sudden death].	2006	17089931
Comparative metabolic capabilities and inhibitory profiles of CYP2D6.1, CYP2D6.10, and CYP2D6.17.	2007 Aug	17470523
Inhibition of astroglial inwardly rectifying Kir4.1 channels by a tricyclic antidepressant, nortriptyline.	2007 Feb	17071817
In silico prediction of pregnane X receptor activators by machine learning approaches.	2007 Jan	17003167
Community-based randomised controlled trial evaluating falls and osteoporosis risk management strategies.	2008 Nov 4	18983670
Citalopram associated with complex visual hallucination: a case report.	2009 Apr 30	19439248
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
Current treatment options in smoking cessation.	2010 Feb	20469625
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 `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

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Name

Type

Language

NORTRIPTYLINE HYDROCHLORIDE

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