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 |
---|---|---|---|---|
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 Date-1.62604794E11 |
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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 Date-1.62604794E11 |
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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 Date-1.62604794E11 |
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 |
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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 |
---|---|---|
Amitriptyline and heart block. | 1967 Jul 29 |
|
Correlation of subjective side effects with plasma concentrations of nortriptyline. | 1970 Oct 3 |
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Tricyclic antidepressants and monoamine oxidase inhibitors. | 1971 Jun |
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Electrocardiographic changes and cardiac arrhythmias in patients receiving psychotropic drugs. | 1976 Feb |
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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 aphonia as a side effect of tricyclic antidepressants. | 1979 Dec |
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Cardiovascular side effects of long-term therapy with tricyclic antidepressants in the aged. | 1979 May |
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Comparison of imipramine- and nortriptyline-induced orthostatic hypotension: a meaningful difference. | 1981 Sep |
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Marked sinus tachycardia resulting from the synergistic effects of marijuana and nortriptyline. | 1983 May |
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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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Tryptophan antagonism of stimulant-induced tics. | 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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Simulated home treatment of depression with nortriptyline. | 1991 |
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Left bundle branch block developing in a patient with sub-therapeutic nortriptyline levels: a case report. | 1991 Oct |
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Cognitive decline with nortriptyline use in a patient with dementia of the Alzheimer's type. | 1992 Jan |
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High initial nortriptyline doses in the treatment of depression. | 1993 Feb |
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Sleep in bereavement-related depression during and after pharmacotherapy with nortriptyline. | 1994 Apr-Jun |
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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 |
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Depression following smoking cessation in women. | 1996 |
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Nortriptyline-induced hepatic failure. | 1996 Feb |
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Extrapyramidal symptoms associated with the adjunct of nortriptyline to a venlafaxine-valproic acid combination. | 1999 May |
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Penetration of amitriptyline, but not of fluoxetine, into brain is enhanced in mice with blood-brain barrier deficiency due to mdr1a P-glycoprotein gene disruption. | 2000 Apr |
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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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Risk factors for falls during treatment of late-life depression. | 2002 Oct |
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The promises and pitfalls of reboxetine. | 2003 Winter |
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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 |
|
Monoamine transporter gene polymorphisms and antidepressant response in koreans with late-life depression. | 2006 Oct 4 |
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In silico prediction of pregnane X receptor activators by machine learning approaches. | 2007 Jan |
|
Tobacco smoking cessation management: integrating varenicline in current practice. | 2008 |
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Nortriptyline protects mitochondria and reduces cerebral ischemia/hypoxia injury. | 2008 Feb |
|
Tako-tsubo syndrome following nortriptyline overdose. | 2008 Jun |
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Possession states precipitated by nortriptyline. | 2008 May |
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Bioactivation of the tricyclic antidepressant amitriptyline and its metabolite nortriptyline to arene oxide intermediates in human liver microsomes and recombinant P450s. | 2008 May 9 |
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Community-based randomised controlled trial evaluating falls and osteoporosis risk management strategies. | 2008 Nov 4 |
|
Trifluoperazine: a rynodine receptor agonist. | 2009 Aug |
|
Spontaneous hypothermia on intensive care unit admission is a predictor of unfavorable neurological outcome in patients after resuscitation: an observational cohort study. | 2010 |
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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 |
|
Current treatment options in smoking cessation. | 2010 Feb |
|
An overview of Indian research in anxiety disorders. | 2010 Jan |
|
Which xenobiotic(s) could be responsible for the radiologic findings below? Answer: any proconvulsant xenobiotic, in this case tramadol, bupropion, and nortriptyline. | 2010 Mar |
|
Profiling of a prescription drug library for potential renal drug-drug interactions mediated by the organic cation transporter 2. | 2011 Jul 14 |
|
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 |
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
Thu Jul 06 21:58:24 UTC 2023
by
admin
on
Thu Jul 06 21:58:24 UTC 2023
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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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Code System | Code | Type | Description | ||
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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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PRIMARY | Merck Index | ||
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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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TRANSPORTER -> SUBSTRATE | |||
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METABOLIC ENZYME -> INHIBITOR |
IC50
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BINDER->LIGAND |
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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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METABOLITE -> PARENT |
MAJOR
PLASMA; URINE
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PARENT -> METABOLITE ACTIVE |
MAJOR
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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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