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

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 PROTRIPTYLINE HYDROCHLORIDE

SMILES

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

InChI

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

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

1967
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
Hypertensive episodes after adding methylphenidate (Ritalin) to tricyclic antidepressants. (Report of three cases and review of clinical advantages).
1972 Jul-Aug
Electrophysiologic studies of perphenazine and protriptyline in a patient with psychotropic drug-induced ventricular fibrillation.
1979 Aug
Seven cases of somnambulism induced by drugs.
1979 Jul
Protriptyline and tinnitus.
1981 Nov
Pharmacologic reversal of hypotensive effect complicating antiarrhythmic therapy with bretylium.
1982 Sep
Bethanechol chloride can reverse erectile and ejaculatory dysfunction induced by tricyclic antidepressants and mazindol: case report.
1986 Apr
The clinical pharmacology of depressive states.
2002 Mar
Diagnosis and treatment of sleep disorders: a brief review for clinicians.
2003 Dec
Current use of selective serotonin reuptake inhibitors and risk of acute myocardial infarction.
2004
Hypersomnia.
2005
The pharmacological management of depression.
2005
Enhancing central noradrenergic function in depression: is there still a place for a new antidepressant?
2005 Mar
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
Drug therapy for obstructive sleep apnoea in adults.
2006 Apr 19
Medical therapy for obstructive sleep apnea: a review by the Medical Therapy for Obstructive Sleep Apnea Task Force of the Standards of Practice Committee of the American Academy of Sleep Medicine.
2006 Aug
Obstructive sleep apnea - management update.
2006 Sep
Prophylaxis of migraine.
2006 Sep
Narcolepsy: treatment issues.
2007
Tricyclic antidepressant poisoning: an evidence-based consensus guideline for out-of-hospital management.
2007
Solid-phase extraction and gas chromatographic- mass spectrometric determination of the veterinary drug xylazine in human blood.
2007 Apr
Antidepressant therapy in tinnitus.
2007 Apr
In silico prediction of pregnane X receptor activators by machine learning approaches.
2007 Jan
Tricyclic antidepressant pharmacology and therapeutic drug interactions updated.
2007 Jul
Toward achieving optimal response: understanding and managing antidepressant side effects.
2008
Psychiatric disorders and traumatic brain injury.
2008 Aug
Prophylaxis of migraine: general principles and patient acceptance.
2008 Dec
Protriptyline block of the human ether-à-go-go-related gene (HERG) K+ channel.
2008 Jan 30
Determination of tricyclic antidepressants in human plasma using pipette tip solid-phase extraction and gas chromatography-mass spectrometry.
2008 Jul
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
Narcolepsy: current treatment options and future approaches.
2008 Jun
cis-4-(Piperazin-1-yl)-5,6,7a,8,9,10,11,11a-octahydrobenzofuro[2,3-h]quinazolin-2-amine (A-987306), a new histamine H4R antagonist that blocks pain responses against carrageenan-induced hyperalgesia.
2008 Nov 27
A novel method for the determination of guanfacine in urine by gas chromatography-mass spectrometry.
2008 Oct
Depression following thrombotic cardiovascular events in elderly medicare beneficiaries: risk of morbidity and mortality.
2009
Obstructive sleep apnea syndrome: from phenotype to genetic basis.
2009 Apr
Pharmacological approaches to the treatment of obstructive sleep apnoea.
2009 May
Association of changes in norepinephrine and serotonin transporter expression with the long-term behavioral effects of antidepressant drugs.
2009 May
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
A cell protection screen reveals potent inhibitors of multiple stages of the hepatitis C virus life cycle.
2010 Feb 23
Research on antidepressants in India.
2010 Jan
The geriatric population and psychiatric medication.
2010 Jan
Trimipraminium maleate.
2010 Jan 16
Niemann-Pick disease type C.
2010 Jun 3
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
In vitro studies of DNA damage caused by tricyclic antidepressants: a role of peroxidase in the side effects of the drugs.
2010 Sep 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 HYDROCHLORIDE
MART.   MI   ORANGE BOOK   USAN   USP   USP-RS   VANDF   WHO-DD  
USAN  
Official Name English
PROTRIPTYLINE HYDROCHLORIDE [ORANGE BOOK]
Common Name English
PROTRIPTYLINE HYDROCHLORIDE [VANDF]
Common Name English
PROTRIPTYLINE HYDROCHLORIDE [MI]
Common Name English
PROTRIPTYLINE HCL
Common Name English
PROTRIPTYLINE HYDROCHLORIDE [USP MONOGRAPH]
Common Name English
PROTRIPTYLINE HYDROCHLORIDE [MART.]
Common Name English
PROTRIPTYLINE HYDROCHLORIDE [USP-RS]
Common Name English
NSC-169912
Code English
Protriptyline hydrochloride [WHO-DD]
Common Name English
PROTRIPTYLINE HYDROCHLORIDE [USAN]
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C94727
Created by admin on Fri Dec 15 15:06:36 GMT 2023 , Edited by admin on Fri Dec 15 15:06:36 GMT 2023
Code System Code Type Description
RS_ITEM_NUM
1580002
Created by admin on Fri Dec 15 15:06:36 GMT 2023 , Edited by admin on Fri Dec 15 15:06:36 GMT 2023
PRIMARY
SMS_ID
100000085117
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PRIMARY
NCI_THESAURUS
C47695
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PRIMARY
RXCUI
203199
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PRIMARY RxNorm
EVMPD
SUB04117MIG
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PRIMARY
EPA CompTox
DTXSID8046951
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PRIMARY
PUBCHEM
14667
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PRIMARY
DRUG BANK
DBSALT001192
Created by admin on Fri Dec 15 15:06:36 GMT 2023 , Edited by admin on Fri Dec 15 15:06:36 GMT 2023
PRIMARY
DAILYMED
44665V00O8
Created by admin on Fri Dec 15 15:06:36 GMT 2023 , Edited by admin on Fri Dec 15 15:06:36 GMT 2023
PRIMARY
ChEMBL
CHEMBL668
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PRIMARY
ECHA (EC/EINECS)
214-956-3
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PRIMARY
CAS
1225-55-4
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PRIMARY
NSC
169912
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PRIMARY
MERCK INDEX
m9280
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PRIMARY Merck Index
CHEBI
8598
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PRIMARY
FDA UNII
44665V00O8
Created by admin on Fri Dec 15 15:06:36 GMT 2023 , Edited by admin on Fri Dec 15 15:06:36 GMT 2023
PRIMARY