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
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
DescriptionCurator'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
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.
CNS Activity
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL222 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26988801 |
2.8 nM [IC50] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | VIVACTIL Approved UseProtriptyline 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 Date1967 |
Cmax
Value | Dose | Co-administered | Analyte | Population |
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14.1 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/639433/ |
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
1448 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/639433/ |
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
74.3 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/639433/ |
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 |
PubMed
Title | Date | PubMed |
---|---|---|
Hypertensive episodes after adding methylphenidate (Ritalin) to tricyclic antidepressants. (Report of three cases and review of clinical advantages). | 1972 Jul-Aug |
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Hypomania and mania after withdrawal of tricyclic antidepressants. | 1981 Jan |
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Protriptyline and tinnitus. | 1981 Nov |
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Pharmacologic reversal of hypotensive effect complicating antiarrhythmic therapy with bretylium. | 1982 Sep |
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Antiarrhythmic action of bethanidine. | 1984 Aug 1 |
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Haloperidol-induced catalepsy: a model for screening antidepressants effective in treatment of depression with Parkinson's disease. | 1997 Dec |
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Pharmacological profile of antidepressants and related compounds at human monoamine transporters. | 1997 Dec 11 |
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The neuropharmacology of upper airway motor control in the awake and asleep states: implications for obstructive sleep apnoea. | 2001 |
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Drug treatments for obstructive sleep apnoea. | 2002 |
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Effects of antidepressants in rats trained to discriminate centrally administered isoproterenol. | 2002 Aug |
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The effects of tricyclic antidepressants on breast cancer risk. | 2002 Jan 7 |
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The clinical pharmacology of depressive states. | 2002 Mar |
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The role of noradrenaline and selective noradrenaline reuptake inhibition in depression. | 2002 Oct |
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Enhancing central noradrenergic function in depression: is there still a place for a new antidepressant? | 2005 Mar |
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Bupropion SR in adults with ADHD: a short-term, placebo-controlled trial. | 2005 Sep |
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Drug therapy for obstructive sleep apnoea in adults. | 2006 Apr 19 |
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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 |
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Prophylaxis of migraine. | 2006 Sep |
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Narcolepsy: treatment issues. | 2007 |
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Antidepressant therapy in tinnitus. | 2007 Apr |
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In silico prediction of pregnane X receptor activators by machine learning approaches. | 2007 Jan |
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Psychiatric disorders and traumatic brain injury. | 2008 Aug |
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Protriptyline block of the human ether-à-go-go-related gene (HERG) K+ channel. | 2008 Jan 30 |
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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 |
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Narcolepsy: current treatment options and future approaches. | 2008 Jun |
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Depression following thrombotic cardiovascular events in elderly medicare beneficiaries: risk of morbidity and mortality. | 2009 |
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Accuracy of Veterans Affairs databases for diagnoses of chronic diseases. | 2009 Oct |
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A cell protection screen reveals potent inhibitors of multiple stages of the hepatitis C virus life cycle. | 2010 Feb 23 |
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Research on antidepressants in India. | 2010 Jan |
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The geriatric population and psychiatric medication. | 2010 Jan |
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Trimipraminium maleate. | 2010 Jan 16 |
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Niemann-Pick disease type C. | 2010 Jun 3 |
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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 |
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
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/20804147
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.
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Classification Tree | Code System | Code | ||
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WHO-ATC |
N06AA11
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N0000175752
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LIVERTOX |
NBK548310
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NCI_THESAURUS |
C94727
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PROTRIPTYLINE
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Protriptyline
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3391
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8886
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4976
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DTXSID0023535
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DB00344
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8597
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4NDU154T12
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C61913
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207-119-9
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100000080857
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ACTIVE MOIETY
METABOLITE (PARENT)
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