Details
Stereochemistry | ACHIRAL |
Molecular Formula | C19H21N |
Molecular Weight | 263.3767 |
Optical Activity | NONE |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
CNCCC=C1C2=C(CCC3=C1C=CC=C3)C=CC=C2
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
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.
CNS Activity
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL222 Sources: https://www.ncbi.nlm.nih.gov/pubmed/10715164 |
6.3 nM [Ki] | ||
Target ID: CHEMBL229 Sources: https://www.ncbi.nlm.nih.gov/pubmed/10447960 |
0.04 nM [IC50] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
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Preventing | AVENTYL HYDROCHLORIDE Approved UseNortriptyline 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 Date1964 |
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Primary | AVENTYL HYDROCHLORIDE Approved UseNortriptyline 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 Date1964 |
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Primary | AVENTYL HYDROCHLORIDE Approved UseNortriptyline 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 Date1964 |
Cmax
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 |
T1/2
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 |
Funbound
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 |
---|---|---|---|
OverviewOther
Other Inhibitor | Other Substrate | Other Inducer |
---|---|---|
Drug as perpetrator
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
Sources: https://pubmed.ncbi.nlm.nih.gov/9574817/ Page: 7.0 |
yes [Ki 450 uM] |
Drug as victim
Target | Modality | Activity | Metabolite | Clinical 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 |
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minor | ||||
minor | ||||
yes |
Tox targets
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
PubMed
Title | Date | PubMed |
---|---|---|
Tricyclic antidepressants and monoamine oxidase inhibitors. | 1971 Jun |
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Urinary retention in a neonate secondary to maternal ingestion of nortriptyline. | 1972 Sep |
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[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 |
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[Double blind clinical study of mianserin and nortriptyline (author's transl)]. | 1978 Sep-Oct |
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Hoarseness and tricyclic antidepressants. | 1980 May |
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Comparison of imipramine- and nortriptyline-induced orthostatic hypotension: a meaningful difference. | 1981 Sep |
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Comparative efficacy and safety of MAOIs versus TCAs in treating depression in the elderly. | 1986 Oct |
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A placebo-controlled comparison of the effect of nortriptyline and phenelzine on orthostatic hypotension in elderly depressed patients. | 1987 Dec |
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The effects of mood changes and antidepressants on the cognitive capacity of elderly depressed patients. | 1989 Fall |
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Tryptophan antagonism of stimulant-induced tics. | 1989 Feb |
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Use of yohimbine to counteract nortriptyline-induced orthostatic hypotension. | 1989 Feb |
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Treatment-emergent depression with antidepressants in panic disorder. | 1989 May-Jun |
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Naproxen reversal of nortriptyline-induced orthostatic hypotension. | 1989 Sep |
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Low dose tricyclic tachycardia. | 1991 Jan |
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Tricyclics and heart failure. | 1991 Nov |
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Drug-induced Creutzfeldt-Jakob like syndrome. | 1992 Sep |
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Downregulation of serotonin receptor subtypes by nortriptyline and adinazolam in major depressive disorder: neuroendocrine and platelet markers. | 1993 |
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High initial nortriptyline doses in the treatment of depression. | 1993 Feb |
|
Sleep in bereavement-related depression during and after pharmacotherapy with nortriptyline. | 1994 Apr-Jun |
|
Depression following smoking cessation in women. | 1996 |
|
A double-blind, placebo-controlled assessment of nortriptyline's side-effects during 3-year maintenance treatment in elderly patients with recurrent major depression. | 1999 Dec |
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Extrapyramidal symptoms associated with the adjunct of nortriptyline to a venlafaxine-valproic acid combination. | 1999 May |
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Evaluation of platelet activation in depressed patients with ischemic heart disease after paroxetine or nortriptyline treatment. | 2000 Apr |
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2-Substituted tryptamines: agents with selectivity for 5-HT(6) serotonin receptors. | 2000 Mar 9 |
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Inhibition of cytochrome P4502D6 activity with paroxetine normalizes the ultrarapid metabolizer phenotype as measured by nortriptyline pharmacokinetics and the debrisoquin test. | 2001 Oct |
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Treatment options for depression and psychosis in Parkinson's disease. | 2001 Sep |
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Risk factors for falls during treatment of late-life depression. | 2002 Oct |
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Optimised procedures for the reversed-phase liquid chromatographic analysis of formulations containing tricyclic antidepressants. | 2003 Apr 24 |
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The promises and pitfalls of reboxetine. | 2003 Winter |
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Efficacy of antidepressants in substance use disorders with and without comorbid depression. A systematic review and meta-analysis. | 2005 Apr 4 |
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Photoinduced chemiluminescence of pharmaceuticals. | 2006 May 3 |
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Nortriptyline delays disease onset in models of chronic neurodegeneration. | 2007 Aug |
|
Possession states precipitated by nortriptyline. | 2008 May |
|
Citalopram associated with complex visual hallucination: a case report. | 2009 Apr 30 |
|
Trifluoperazine: a rynodine receptor agonist. | 2009 Aug |
|
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 |
|
Profiling of a prescription drug library for potential renal drug-drug interactions mediated by the organic cation transporter 2. | 2011 Jul 14 |
Sample Use Guides
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/21897201
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
Edited
Sat Dec 16 16:29:26 GMT 2023
by
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on
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Record UNII |
BL03SY4LXB
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Record Status |
Validated (UNII)
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Record Version |
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Classification Tree | Code System | Code | ||
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NCI_THESAURUS |
C94727
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LIVERTOX |
NBK548526
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WHO-ATC |
N06AA10
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NDF-RT |
N0000175752
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WHO-VATC |
QN06AA10
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757234
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Nortriptyline
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1328
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BL03SY4LXB
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3371
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DTXSID9023384
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72-69-5
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2404
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200-788-8
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NORTRIPTYLINE
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m8074
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1971
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C62060
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CHEMBL445
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7531
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BL03SY4LXB
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D009661
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SUB09380MIG
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DB00540
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7640
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100000083622
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4543
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Related Record | Type | Details | ||
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METABOLIC ENZYME -> SUBSTRATE |
Metabolizing reaction by CYP2D6: 2-Hydroxylation
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TARGET -> INHIBITOR | |||
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METABOLIC ENZYME -> INHIBITOR |
IC50
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BINDER->LIGAND |
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TRANSPORTER -> SUBSTRATE | |||
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METABOLIC ENZYME -> SUBSTRATE |
Pharmacological action: Tricyclic antidepressant drug (TCA)
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SALT/SOLVATE -> PARENT |
Related Record | Type | Details | ||
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PARENT -> METABOLITE ACTIVE |
MAJOR
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METABOLITE -> PARENT |
MAJOR
PLASMA; URINE
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METABOLITE -> PARENT |
MINOR
PLASMA; URINE
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Related Record | Type | Details | ||
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PARENT -> IMPURITY |
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
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Related Record | Type | Details | ||
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ACTIVE MOIETY |
Name | Property Type | Amount | Referenced Substance | Defining | Parameters | References |
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Biological Half-life | PHARMACOKINETIC |
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