World Library  
Flag as Inappropriate
Email this Article


Article Id: WHEBN0005901072
Reproduction Date:

Title: Protriptyline  
Author: World Heritage Encyclopedia
Language: English
Subject: Butriptyline, Dosulepin, Lofepramine, Iprindole, Tricyclic antidepressant
Collection: Amines, Dibenzocycloheptenes, Tricyclic Antidepressants
Publisher: World Heritage Encyclopedia


Systematic (IUPAC) name
Clinical data
Trade names Vivactil
  • US: C (Risk not ruled out)
Legal status
  • (Prescription only)
Routes of
Pharmacokinetic data
Metabolism Hepatic
Biological half-life 54-92 hours
Excretion Urine
CAS Registry Number  Y
ATC code N06
PubChem CID:
DrugBank  Y
ChemSpider  Y
Chemical data
Formula C19H21N
Molecular mass 263.377 g/mol

Protriptyline (Vivactil) is a tricyclic antidepressant (TCA), specifically a secondary amine, indicated for the treatment of depression and ADHD. Unique among the TCAs, protriptyline tends to be energizing instead of sedating, and is sometimes used for narcolepsy to achieve a wakefulness-promoting effect.

TCAs including protriptyline are also used to reduce the incidence of recurring headaches such as migraine, and for other types of chronic pain. This drug can also be used for sleep apnea treatment along with a carbonic anhydrase inhibitor.

Its sale was discontinued in the UK, Australia, and Republic of Ireland in 2000.[1]


  • Purpose 1
  • Description 2
  • Mechanism of action 3
  • Withdrawal 4
  • Recommended dosage 5
  • Precautions 6
  • Side effects 7
  • Adverse reactions 8
  • Overdose 9
  • Metabolism 10
  • References 11


Protriptyline is used primarily to treat depression and to treat the combination of symptoms of anxiety and depression.[2] 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.[3]


Protriptyline hydrochloride, a dibenzocycloheptene derivative, has a molecular weight of 299.84 g/mol.[2] It is a white to yellowish powder that is freely soluble in water and soluble in dilute HCl. Protriptyline hydrochloride is supplied as 5 mg or 10 mg tablets.[2] Inactive ingredients are anhydrous lactose, colloidal silicon dioxide, magnesium stearate, and microcrystalline cellulose.[3]

Mechanism of action

Protriptyline acts by decreasing the reuptake of norepinephrine and to a lesser extent serotonin (5-HT) in the brain.[4] 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.[4] 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.[4]

Protriptyline is a tricyclic antidepressant.[5] It was thought that tricyclic antidepressants work by inhibiting the re-uptake of the neurotransmitters norepinephrine and serotonin by nerve cells.[5] However, this response occurs immediately, yet mood does not lift for around two weeks.[5] It is now thought that changes occur in receptor sensitivity in the cerebral cortex and hippocampus.[5] The hippocampus is part of the limbic system, a part of the brain involved in emotions. Presynaptic receptors are affected: a1 and b1 receptors are sensitized, a2 receptors are desensitised (leading to increased noradrenaline production).[5] Tricyclics are also known as effective analgesics for different types of pain, especially neuropathic or neuralgic pain.[5] A precise mechanism for their analgesic action is unknown, but it is thought that they modulate anti-pain opioid systems in the CNS via an indirect serotonergic route. They are also effective in migraine prophylaxis, but not in abortion of acute migraine attack.[5] The mechanism of their anti-migraine action is also thought to be serotonergic.[5]


Though not indicative of addiction, abrupt cessation of treatment after prolonged therapy may produce nausea, headache, and malaise.[4]

Recommended dosage

Protriptyline is available as 5 mg and 10 mg tablets.[5] Doses range from 15 to 40 mg per day and can be taken in one daily dose or divided into up to four doses daily.[5] Some people with severe depression may require up to 60 mg per day.[5] In adolescents and people over age 60, therapy should be initiated at a dose of 5 mg three times a day and increased under supervision of a physician as needed.[5] Patients over age 60 who are taking daily doses of 20 mg or more should be closely monitored for side effects such as rapid heart rate and urinary retention.[5]


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.[6] 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.[6] Its side effects are especially noticeable early in therapy.[6] 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.[7] 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 anti-depressants including SSRIs, SNRIs or MonoAmineOxidase Inhibitors.[7] It may be dangerous to take protriptyline in combination with these substances.[7] Protriptyline may increase the possibility of having seizures.[7]

Protriptyline may increase heart rate and stress on the heart.[4] It may be dangerous for people with cardiovascular disease, especially those who have recently had a heart attack, to take this drug or other antidepressants in the same pharmacological class.[4] In rare cases in which patients with cardiovascular disease must take protriptyline, they should be monitored closely for cardiac rhythm disturbances and signs of cardiac stress or damage.[4] When Protriptyline is used to treat the depressive component of schizophrenia, psychotic symptoms may be aggravated. Likewise, in manic-depressive psychosis, depressed patients may experience a shift toward the manic phase if they are treated with an antidepressant drug. Paranoid delusions, with or without associated hostility, may be exaggerated.[5] In any of these circumstances, it may be advisable to reduce the dose of Protriptyline or to use a major tranquilizing drug concurrently.[5]

Side effects

Protriptyline shares side effects common to all tricyclic antidepressants.[2] The most frequent of these are dry mouth, constipation, urinary retention, increased heart rate, sedation, irritability, dizziness, decreased coordination, anxiety, blood disorders, confusion, decreased libido, dizziness, flushing, headache, impotence, insomnia, low blood pressure, nightmares, rapid or irregular heartbeat, rash, seizures, sensitivity to sunlight, stomach and intestinal problems.[5] Other more complicated side effects include; chest pain or heavy feeling, pain spreading to the arm or shoulder, nausea, sweating, general ill feeling; sudden numbness or weakness, especially on one side of the body; sudden headache, confusion, problems with vision, speech, or balance; hallucinations, or seizure (convulsions); easy bruising or bleeding, unusual weakness; restless muscle movements in your eyes, tongue, jaw, or neck; urinating less than usual or not at all; extreme thirst with headache, nausea, vomiting, and weakness; or feeling light-headed or fainting.[5]

Dry mouth, if severe to the point of causing difficulty speaking or swallowing, may be managed by dosage reduction or temporary discontinuation of the drug.[2] Patients may also chew sugarless gum or suck on sugarless candy in order to increase the flow of saliva. Some artificial saliva products may give temporary relief.[2] Men with prostate enlargement who take protriptyline may be especially likely to have problems with urinary retention.[5] Symptoms include having difficulty starting a urine flow and more difficulty than usual passing urine.[5] In most cases, urinary retention is managed with dose reduction or by switching to another type of antidepressant.[5] In extreme cases, patients may require treatment with bethanechol, a drug that reverses this particular side effect.[5]

Adverse reactions

Cardiovascular: Myocardial infarction; stroke; heart block; arrhythmias; hypotension, particularly orthostatic hypotension; hypertension; tachycardia; palpitation.[8]

Psychiatric: Confusional states (especially in the elderly) with hallucinations, disorientation, delusions, anxiety, restlessness, agitation; hypomania; exacerbation of psychosis; insomnia, panic, and nightmares.[2]

Neurological: Seizures; incoordination; ataxia; tremors; peripheral neuropathy; numbness, tingling, and paresthesias of extremities; extrapyramidal symptoms; drowsiness; dizziness; weakness and fatigue; headache; syndrome of inappropriate ADH (antidiuretic hormone) secretion;tinnitus; alteration in EEG patterns.[2]

Anticholinergic: Paralytic ileus; hyperpyrexia; urinary retention, delayed micturition, dilatation of the urinary tract; constipation; blurred vision, disturbance of accommodation, increased intraocular pressure, mydriasis; dry mouth and rarely associated sublingual adentitis.[2]

Allergic: Drug fever; petechiae, skin rash, urticaria, itching, photosensitization (avoid excessive exposure to sunlight); edema (general, or of face and tongue).[2]

Hematologic: Agranulocytosis; bone marrow depression; leukopenia;thrombocytopenia; purpura; eosinophilia.[2]

Gastrointestinal: Nausea and vomiting; anorexia; epigastric distress; diarrhea; peculiar taste; stomatitis; abdominal cramps; black tongue.[2]

Endocrine: Impotence, increased or decreased libido: gynecomastia in the male; breast enlargement and galactorrhea in the female; testicular swelling; elevation or depression of blood sugar levels.[2]

Other: Jaundice (simulating obstructive); altered liver function; parotid swelling; alopecia; flushing; weight gain or loss; urinary frequency, nocturia; perspiration.[2]


Deaths may occur from overdosage with this class of drugs.[7] Multiple drug ingestion (including alcohol) is common in deliberate tricyclic antidepressant overdose.[7] As management of overdose is complex and changing, it is recommended that the physician contact a poison control center for current information on treatment.[2] Signs and symptoms of toxicity develop rapidly after tricyclic antidepressant overdose, therefore, hospital monitoring is required as soon as possible.[7] Critical manifestations of overdosage include: cardiac dysrhythmias, severe hypotension, convulsions, and CNS depression, including coma.[5] Changes in the electrocardiogram, particularly in QRS axis or width, are clinically significant indicators of tricyclic antidepressant toxicity.[5] Other signs of overdose may include: confusion, disturbed concentration, transient visual hallucinations, dilated pupils, agitation, hyperactive reflexes, stupor, drowsiness, muscle rigidity, vomiting, hypothermia, hyperpyrexia.[5]


Metabolic studies indicate that Protriptyline is well absorbed from the gastrointestinal tract and is rapidly sequestered in tissues.[2] Relatively low plasma levels are found after administration, and only a small amount of unchanged drug is excreted in the urine of dogs and rabbits.[2] Preliminary studies indicate that demethylation of the secondary amine moiety occurs to a significant extent, and that metabolic transformation takes place in the liver.[2] It penetrates the brain rapidly in mice and rats, and moreover that which is present in the brain is almost all unchanged drug.[2] Studies on the disposition of radioactive Protriptyline in human test subjects showed significant plasma levels within 2 hours, peaking at 8 to 12 hours, then declining gradually.[2] Urinary excretion studies in the same subjects showed significant amounts of radioactivity in 2 hours.[2] The rate of excretion was slow.[2] Cumulative urinary excretion during 16 days accounted for approximately 50% of the drug. The fecal route of excretion did not seem to be important.[2]


  1. ^
  2. ^ a b c d e f g h i j k l m n o p q r s t u v w DURAMED PHARMACEUTICALS, INC., . (Ed.). (2007). Protriptyline drug facts. Pomona, New York : Barr Pharmaceuticals, Inc.
  3. ^ a b ULTRAM, . (Ed.). (2007). Protriptyline. Ortho-McNeil Pharmaceutical Inc.
  4. ^ a b c d e f g Advameg, Inc. (2010). Protriptyline at
  5. ^ a b c d e f g h i j k l m n o p q r s t u v w x American Society of Health-System Pharmacists. AHFS Drug Information 2002. Bethesda: American Society of Health-System Pharmacists, 2002.
  6. ^ a b c Kirchheiner, J; Nickchen, K; Bauer, M; Wong, M-L; Licinio, J; Roots, I; Brockmöller, J (May 2004). "Pharmacogenetics of antidepressants and antipsychotics: the contribution of allelic variations to the phenotype of drug response". Mol. Psychiatry 9 (5): 442–73.  
  7. ^ a b c d e f g DeVane, C. Lindsay, Pharm.D. "Drug Therapy for Mood Disorders." In Fundamentals of Monitoring Psychoactive Drug Therapy. Baltimore: Williams and Wilkins, 1990.
  8. ^ Sériès F, Cormier Y (October 1990). "Effects of protriptyline on diurnal and nocturnal oxygenation in patients with chronic obstructive pulmonary disease". Ann. Intern. Med. 113 (7): 507–11.  
This article was sourced from Creative Commons Attribution-ShareAlike License; additional terms may apply. World Heritage Encyclopedia content is assembled from numerous content providers, Open Access Publishing, and in compliance with The Fair Access to Science and Technology Research Act (FASTR), Wikimedia Foundation, Inc., Public Library of Science, The Encyclopedia of Life, Open Book Publishers (OBP), PubMed, U.S. National Library of Medicine, National Center for Biotechnology Information, U.S. National Library of Medicine, National Institutes of Health (NIH), U.S. Department of Health & Human Services, and, which sources content from all federal, state, local, tribal, and territorial government publication portals (.gov, .mil, .edu). Funding for and content contributors is made possible from the U.S. Congress, E-Government Act of 2002.
Crowd sourced content that is contributed to World Heritage Encyclopedia is peer reviewed and edited by our editorial staff to ensure quality scholarly research articles.
By using this site, you agree to the Terms of Use and Privacy Policy. World Heritage Encyclopedia™ is a registered trademark of the World Public Library Association, a non-profit organization.

Copyright © World Library Foundation. All rights reserved. eBooks from Project Gutenberg are sponsored by the World Library Foundation,
a 501c(4) Member's Support Non-Profit Organization, and is NOT affiliated with any governmental agency or department.