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
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
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 |
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 |
---|---|---|---|
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 |
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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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Ophthalmological effects of nortriptyline--relationship to plasma level. | 1972 |
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Ototoxic reaction associated with use of nortriptyline hydrochloride: case report. | 1972 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 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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Hoarseness and tricyclic antidepressants. | 1980 May |
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Atrial flutter with amoxapine: a case report. | 1981 Nov |
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Comparison of imipramine- and nortriptyline-induced orthostatic hypotension: a meaningful difference. | 1981 Sep |
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The clinical efficacy and side-effects of mianserin and nortriptyline in depressed out-patients: a double-blind randomized trial. | 1982 |
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Marked sinus tachycardia resulting from the synergistic effects of marijuana and nortriptyline. | 1983 May |
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Psychosis after discontinuation of nortriptyline. | 1984 Apr |
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The antiarrhythmic effect of nortriptyline in cardiac patients with ventricular premature depolarizations. | 1986 Jun |
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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 |
|
Occurrence of myoclonus in patients treated with cyclic antidepressants. | 1987 Mar |
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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 |
|
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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Myoclonus caused by a tricyclic antidepressant. | 1990 Apr |
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Simulated home treatment of depression with nortriptyline. | 1991 |
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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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Recurrent hypotension immediately after seizures in nortriptyline overdose. | 1994 Jul |
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The cardiovascular effects of bupropion and nortriptyline in depressed outpatients. | 1994 Jun |
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Nortriptyline-induced fulminant hepatic failure. | 1995 Jan |
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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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[A case of Brugada syndrome with convulsive seizure during antidepressant administration: relation of antidepressant agents and arrhythmia leading to sudden death]. | 2006 |
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Monoamine transporter gene polymorphisms and antidepressant response in koreans with late-life depression. | 2006 Oct 4 |
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Inhibition of astroglial inwardly rectifying Kir4.1 channels by a tricyclic antidepressant, nortriptyline. | 2007 Feb |
|
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 |
|
Adverse reactions to antidepressants. | 2009 Sep |
|
A new strategy for antidepressant prescription. | 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 |
|
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
Fri Jun 25 21:56:48 UTC 2021
by
admin
on
Fri Jun 25 21:56:48 UTC 2021
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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 |
700
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WHO-ATC |
N06AA10
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NDF-RT |
N0000175752
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WHO-VATC |
QN06AA10
Created by
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Code System | Code | Type | Description | ||
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Nortriptyline
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1328
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PRIMARY | |||
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BL03SY4LXB
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PRIMARY | |||
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3371
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PRIMARY | |||
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72-69-5
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PRIMARY | |||
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72-69-5
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PRIMARY | |||
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2404
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PRIMARY | |||
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200-788-8
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PRIMARY | |||
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NORTRIPTYLINE
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PRIMARY | |||
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M8074
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PRIMARY | Merck Index | ||
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1971
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PRIMARY | |||
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C62060
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PRIMARY | |||
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CHEMBL445
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PRIMARY | |||
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7531
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PRIMARY | RxNorm | ||
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D009661
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SUB09380MIG
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DB00540
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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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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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