U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

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
Structure of PROTRIPTYLINE

SMILES

CNCCCC1C2=C(C=CC=C2)C=CC3=C1C=CC=C3

InChI

InChIKey=BWPIARFWQZKAIA-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/h2-5,7-10,12-13,19-20H,6,11,14H2,1H3

HIDE SMILES / InChI

Description
Curator's Comment: description was created based on several sources, including https://www.drugbank.ca/drugs/DB00344 | https://www.drugs.com/pro/protriptyline.html | http://reference.medscape.com/drug/vivactil-protriptyline-342945 | https://www.ncbi.nlm.nih.gov/pubmed/26988801 | https://www.ncbi.nlm.nih.gov/pubmed/20804147

Protriptyline (trade name Vivactil) is a tricyclic antidepressant, indicated for the treatment of depression. Protriptyline acts by decreasing the reuptake of norepinephrine and to a lesser extent serotonin (5-HT) in the brain. Tricyclic antidepressants act to change the balance of naturally occurring chemicals in the brain that regulate the transmission of nerve impulses between cells. Protriptyline increases the concentration of norepinephrine and serotonin (both chemicals that stimulate nerve cells) and, to a lesser extent, blocks the action of another brain chemical, acetylcholine. The therapeutic effects of protriptyline, like other antidepressants, appear slowly. Maximum benefit is often not evident for at least two weeks after starting the drug. Protriptyline is used primarily to treat depression and to treat the combination of symptoms of anxiety and depression. Like most antidepressants of this chemical and pharmacological class, protriptyline has also been used in limited numbers of patients to treat panic disorder, obsessive-compulsive disorder, attention-deficit/hyperactivity disorder, enuresis, eating disorders such as bulimia nervosa, cocaine dependency, and the depressive phase of bipolar disorder (manic-depressive) disorder. It has also been used to support smoking cessation programs. Like all tricyclic antidepressants, protriptyline should be used cautiously and with close physician supervision. This is especially so in the elderly, or people who have benign prostatic hypertrophy (enlarged prostate gland), or urinary retention, or glaucoma, especially angle-closure glaucoma (the most severe form). Before starting treatment, people should discuss the relative risks and benefits of treatment with their doctors to help determine if protriptyline is the right antidepressant for them. A common problem with tricyclic antidepressants is sedation (drowsiness, lack of physical and mental alertness), but protriptyline is considered the least sedating agent among this class of agents. Its side effects are especially noticeable early in therapy. In most people, early tricyclic side-effects decrease or disappear entirely with time, but, until then, patients taking protriptyline should take care to assess which side-effects occur in them and should not perform hazardous activities requiring mental acuity or coordination. The side-effects are increased when protriptyline is taken with central nervous system depressants, such as alcoholic beverages, sleeping medications, other sedatives, or antihistamines, as well as with other antidepressants including SSRIs, SNRIs or monoamine oxidase Inhibitors.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
2.8 nM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
VIVACTIL

Approved Use

Protriptyline Hydrochloride Tablets, USP are indicated for the treatment of symptoms of mental depression in patients who are under close medical supervision. Its activating properties make it particularly suitable for withdrawn and anergic patients.

Launch Date

-7.1452803E10
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
14.1 ng/mL
30 mg single, oral
dose: 30 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
PROTRIPTYLINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
1448 ng × h/mL
30 mg single, oral
dose: 30 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
PROTRIPTYLINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
74.3 h
30 mg single, oral
dose: 30 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
PROTRIPTYLINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
60 mg 1 times / day multiple, oral
Highest studied dose
Dose: 60 mg, 1 times / day
Route: oral
Route: multiple
Dose: 60 mg, 1 times / day
Sources:
unhealthy
Health Status: unhealthy
Condition: mental depression
Sex: unknown
Sources:
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG

OverviewOther

Other InhibitorOther SubstrateOther Inducer

Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
yes
Tox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
PubMed

PubMed

TitleDatePubMed
Iatrogenic epilepsy due to antidepressant drugs.
1969 Oct 11
Seven cases of somnambulism induced by drugs.
1979 Jul
Hypomania and mania after withdrawal of tricyclic antidepressants.
1981 Jan
Protriptyline and tinnitus.
1981 Nov
Monoaminergic mechanisms and experimental cataplexy.
1981 Oct
Pharmacologic reversal of hypotensive effect complicating antiarrhythmic therapy with bretylium.
1982 Sep
Antiarrhythmic action of bethanidine.
1984 Aug 1
Antiarrhythmic and electrophysiologic actions of bethanidine sulfate in primary ventricular fibrillation or life-threatening ventricular tachycardia.
1984 May 1
Bethanechol chloride can reverse erectile and ejaculatory dysfunction induced by tricyclic antidepressants and mazindol: case report.
1986 Apr
Haloperidol-induced catalepsy: a model for screening antidepressants effective in treatment of depression with Parkinson's disease.
1997 Dec
Pharmacological profile of antidepressants and related compounds at human monoamine transporters.
1997 Dec 11
The neuropharmacology of upper airway motor control in the awake and asleep states: implications for obstructive sleep apnoea.
2001
High-performance liquid chromatographic analysis for a non-chromophore-containing phosphatidyl inositol analog, 1-((1-O-octadecyl-2-O-methyl-sn-glycero)phospho)-1D-3-deoxy-myo-inositol, using indirect UV detection.
2001 Apr 13
Drug treatments for obstructive sleep apnoea.
2002
Effects of antidepressants in rats trained to discriminate centrally administered isoproterenol.
2002 Aug
Painful ejaculation and urinary hesitancy in association with antidepressant therapy: relief with tamsulosin.
2002 Aug
The effects of tricyclic antidepressants on breast cancer risk.
2002 Jan 7
The role of noradrenaline and selective noradrenaline reuptake inhibition in depression.
2002 Oct
Diagnosis and treatment of sleep disorders: a brief review for clinicians.
2003 Dec
Behavioral and pharmacologic therapy of obstructive sleep apnea.
2003 Jun
Tricyclic antidepressants as long-acting local anesthetics.
2003 May
Current use of selective serotonin reuptake inhibitors and risk of acute myocardial infarction.
2004
Pharmacotherapies for obstructive sleep apnoea: where are we now?
2004
Intrathecal tri-cyclic antidepressants produce spinal anesthesia.
2004 Nov
Antidepressant medication use among First Nations peoples residing within British Columbia.
2004 Nov 5
Risk of fetal exposure to tricyclic antidepressants.
2004 Oct
Hypersomnia.
2005
The pharmacological management of depression.
2005
Bupropion SR in adults with ADHD: a short-term, placebo-controlled trial.
2005 Sep
Use of antidepressant medications in relation to the incidence of breast cancer.
2006 Apr 10
Obstructive sleep apnea - management update.
2006 Sep
Prophylaxis of migraine.
2006 Sep
Narcolepsy: treatment issues.
2007
Solid-phase extraction and gas chromatographic- mass spectrometric determination of the veterinary drug xylazine in human blood.
2007 Apr
Tricyclic antidepressant pharmacology and therapeutic drug interactions updated.
2007 Jul
Prophylaxis of migraine: general principles and patient acceptance.
2008 Dec
Atomoxetine improves sleepiness and global severity of illness but not the respiratory disturbance index in mild to moderate obstructive sleep apnea with sleepiness.
2008 Jul
Obstructive sleep apnea syndrome: from phenotype to genetic basis.
2009 Apr
Accuracy of Veterans Affairs databases for diagnoses of chronic diseases.
2009 Oct
Drugs associated with more suicidal ideations are also associated with more suicide attempts.
2009 Oct 2
Development of a list of potentially inappropriate drugs for the korean elderly using the delphi method.
2010 Dec
Antidepressant drugs in oral fluid using liquid chromatography-tandem mass spectrometry.
2010 Mar
Tricyclic antidepressants and headaches: systematic review and meta-analysis.
2010 Oct 20
First-in-class, dual-action, 3,5-disubstituted indole derivatives having human nitric oxide synthase (nNOS) and norepinephrine reuptake inhibitory (NERI) activity for the treatment of neuropathic pain.
2012 Apr 12
A class of tricyclic compounds blocking malaria parasite oocyst development and transmission.
2013 Jan
Patents

Sample Use Guides

Usual Adult Dosage Fifteen to 40 mg a day divided into 3 or 4 doses. If necessary, dosage may be increased to 60 mg a day. Dosages above this amount are not recommended. Increases should be made in the morning dose.
Route of Administration: Oral
The standard reaction mixture with calf thymus DNA contained (unless otherwise specified) 0.2 μM HRP, 13 μM per bp calf thymus DNA (∼10 ng/μL), 500 μM Protriptyline, and 500 μM H2O2 in Sorenson buffer (pH 7.0) containing 67 mM dibasic sodium phosphate and 67 mM monobasic potassium phosphate. The standard reaction mixture with pBR322 plasmid contained 0.2 μM HRP, 3 ng/μL (∼5 μM per bp) plasmid, 500 μM Protriptyline, and 500 μMH2O2 in 67 mM Sorenson buffer (pH 7.0). The volume of the reaction mixtures prepared for the 15-well gels was 10 μL; the volume of the reactions prepared for 8-well gels was 20 μL. The components were added in the order listed. All reaction mixtures were incubated at 37 C for 1 h in a water bath.
Name Type Language
PROTRIPTYLINE
HSDB   INN   MI   VANDF   WHO-DD  
INN  
Official Name English
VIVACTIL
Brand Name English
MK-240
Code English
PROTRIPTYLINE [WHO-DD]
Common Name English
protriptyline [INN]
Common Name English
PROTRIPTYLINE [VANDF]
Common Name English
5H-DIBENZO(A,D)CYCLOHEPTENE-5-PROPANAMINE, N-METHYL-, HYDROCHLORIDE
Systematic Name English
PROTRIPTYLINE [MI]
Common Name English
N-METHYL-5H-DIBENZO(A,D)CYCLOHEPTENE-5-PROPYLAMINE HYDROCHLORIDE
Systematic Name English
PROTRIPTYLINE [HSDB]
Common Name English
Classification Tree Code System Code
WHO-ATC N06AA11
Created by admin on Fri Dec 15 18:48:39 UTC 2023 , Edited by admin on Fri Dec 15 18:48:39 UTC 2023
NDF-RT N0000175752
Created by admin on Fri Dec 15 18:48:39 UTC 2023 , Edited by admin on Fri Dec 15 18:48:39 UTC 2023
LIVERTOX NBK548310
Created by admin on Fri Dec 15 18:48:39 UTC 2023 , Edited by admin on Fri Dec 15 18:48:39 UTC 2023
WHO-VATC QN06AA11
Created by admin on Fri Dec 15 18:48:39 UTC 2023 , Edited by admin on Fri Dec 15 18:48:39 UTC 2023
NCI_THESAURUS C94727
Created by admin on Fri Dec 15 18:48:39 UTC 2023 , Edited by admin on Fri Dec 15 18:48:39 UTC 2023
Code System Code Type Description
MESH
D011530
Created by admin on Fri Dec 15 18:48:39 UTC 2023 , Edited by admin on Fri Dec 15 18:48:39 UTC 2023
PRIMARY
INN
1663
Created by admin on Fri Dec 15 18:48:39 UTC 2023 , Edited by admin on Fri Dec 15 18:48:39 UTC 2023
PRIMARY
WIKIPEDIA
PROTRIPTYLINE
Created by admin on Fri Dec 15 18:48:39 UTC 2023 , Edited by admin on Fri Dec 15 18:48:39 UTC 2023
PRIMARY
IUPHAR
7285
Created by admin on Fri Dec 15 18:48:39 UTC 2023 , Edited by admin on Fri Dec 15 18:48:39 UTC 2023
PRIMARY
DAILYMED
4NDU154T12
Created by admin on Fri Dec 15 18:48:39 UTC 2023 , Edited by admin on Fri Dec 15 18:48:39 UTC 2023
PRIMARY
LACTMED
Protriptyline
Created by admin on Fri Dec 15 18:48:39 UTC 2023 , Edited by admin on Fri Dec 15 18:48:39 UTC 2023
PRIMARY
ChEMBL
CHEMBL668
Created by admin on Fri Dec 15 18:48:39 UTC 2023 , Edited by admin on Fri Dec 15 18:48:39 UTC 2023
PRIMARY
MERCK INDEX
m9280
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PRIMARY Merck Index
HSDB
3391
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PRIMARY
RXCUI
8886
Created by admin on Fri Dec 15 18:48:39 UTC 2023 , Edited by admin on Fri Dec 15 18:48:39 UTC 2023
PRIMARY RxNorm
PUBCHEM
4976
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PRIMARY
EVMPD
SUB10145MIG
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PRIMARY
CAS
438-60-8
Created by admin on Fri Dec 15 18:48:39 UTC 2023 , Edited by admin on Fri Dec 15 18:48:39 UTC 2023
PRIMARY
DRUG CENTRAL
2320
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PRIMARY
CHEBI
8598
Created by admin on Fri Dec 15 18:48:39 UTC 2023 , Edited by admin on Fri Dec 15 18:48:39 UTC 2023
PRIMARY
EPA CompTox
DTXSID0023535
Created by admin on Fri Dec 15 18:48:39 UTC 2023 , Edited by admin on Fri Dec 15 18:48:39 UTC 2023
PRIMARY
DRUG BANK
DB00344
Created by admin on Fri Dec 15 18:48:39 UTC 2023 , Edited by admin on Fri Dec 15 18:48:39 UTC 2023
PRIMARY
CHEBI
8597
Created by admin on Fri Dec 15 18:48:39 UTC 2023 , Edited by admin on Fri Dec 15 18:48:39 UTC 2023
PRIMARY
FDA UNII
4NDU154T12
Created by admin on Fri Dec 15 18:48:39 UTC 2023 , Edited by admin on Fri Dec 15 18:48:39 UTC 2023
PRIMARY
NCI_THESAURUS
C61913
Created by admin on Fri Dec 15 18:48:39 UTC 2023 , Edited by admin on Fri Dec 15 18:48:39 UTC 2023
PRIMARY
ECHA (EC/EINECS)
207-119-9
Created by admin on Fri Dec 15 18:48:39 UTC 2023 , Edited by admin on Fri Dec 15 18:48:39 UTC 2023
PRIMARY
SMS_ID
100000080857
Created by admin on Fri Dec 15 18:48:39 UTC 2023 , Edited by admin on Fri Dec 15 18:48:39 UTC 2023
PRIMARY