Protriptyline

Source: Wikipedia, the free encyclopedia.
Protriptyline
Clinical data
Trade namesVivactyl, others
Other namesAmimethyline; Protriptyline hydrochloride; MK-240
AHFS/Drugs.comMonograph
MedlinePlusa604025
Routes of
administration		Oral
ATC code
Legal status
Legal status
  • BR: Class C1 (Other controlled substances)[1]
  • In general: ℞ (Prescription only)
Hepatic
Elimination half-life54–92 hours
ExcretionUrine: 50%[2]
Feces: minor[2]
Identifiers
  • 3-(5H-dibenzo[a,d][7]annulen-5-yl)-N-methylpropan-1-amine
JSmol)
  • c3cc2c(\C=C/c1c(cccc1)C2CCCNC)cc3
  • 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 checkY
  • Key:BWPIARFWQZKAIA-UHFFFAOYSA-N checkY
  (verify)

Protriptyline, sold under the brand name Vivactil among others, is 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.

Medical uses

Protriptyline is used primarily to treat

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.[4]

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 TCAs, protriptyline should be used cautiously and with close physician supervision. This is especially so for persons with

benign prostatic hypertrophy (enlarged prostate gland), and for the elderly. 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]

Contraindications

Protriptyline may increase heart rate and stress on the heart.[7] 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.[7] 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.[7]

When protriptyline is used to treat the depressive component of

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 an antipsychotic drug concurrently.[5]

Side effects

Protriptyline shares side effects common to all TCAs.

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.[3] 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.[3] 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]

A common problem with TCAs 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 TCA 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.[8] Protriptyline may increase the possibility of having seizures.[8]

Withdrawal

Though not indicative of addiction, abrupt cessation of treatment after prolonged therapy may produce nausea, headache, and malaise.[7]

List of side effects

Overdose

Main article: Tricyclic antidepressant overdose

Deaths may occur from

overdose with this class of drugs.[8] Multiple drug ingestion (including alcohol) is common in deliberate TCA overdose.[8] As management of overdose is complex and changing, it is recommended that the physician contact a poison control center for current information on treatment.[3] Signs and symptoms of toxicity develop rapidly after TCA overdose, therefore, hospital monitoring is required as soon as possible.[8]

Critical manifestations of overdose 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 TCA toxicity.[5]
Other signs of overdose may include: confusion, disturbed concentration, transient visual hallucinations, dilated pupils, agitation, hyperactive reflexes,
hyperpyrexia.[5]

Interactions

The side effects of protriptyline are increased when it 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.[8] It may be dangerous to take protriptyline in combination with these substances.[8]

Pharmacology

Pharmacodynamics

See also: Pharmacology of antidepressants and Tricyclic antidepressant § Binding profiles
Protriptyline[10]
Site Ki (nM) Species Ref
SERTTooltip Serotonin transporter 19.6 Human [11]
NETTooltip Norepinephrine transporter 1.41 Human [11]
DATTooltip Dopamine transporter 2,100 Human [11]
5-HT1A 3,800 Human [12]
5-HT2A 70 Human [12]
5-HT2C ND ND ND
α1 130 Human [13]
α2 6,600 Human [13]
β
 >10,000 Monkey/rat [14]
D2
 2,300 Human [13]
H1 7.2–25 Human [15][13]
H2 398 Human [15]
H3 >100,000 Human [15]
H4 15,100 Human [15]
mAChTooltip Muscarinic acetylcholine receptor 25 Human [13][16]
Values are Ki (nM). The smaller the value, the more strongly the drug binds to the site.

Protriptyline acts by decreasing the

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.[7] 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.[7]

Protriptyline is a TCA.

prophylaxis, but not in abortion of acute migraine attack.[5] The mechanism of their anti-migraine action is also thought to be serotonergic, similar to psilocybin.[5]

Pharmacokinetics

Metabolic studies indicate that protriptyline is well absorbed from the gastrointestinal tract and is rapidly sequestered in tissues.[3] 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.[3] Preliminary studies indicate that demethylation of the secondary amine moiety occurs to a significant extent, and that metabolic transformation takes place in the liver.[3] It penetrates the brain rapidly in mice and rats, and moreover that which is present in the brain is almost all unchanged drug.[3] 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.[3]

Urinary excretion studies in the same subjects showed significant amounts of radioactivity in 2 hours.[3] The rate of excretion was slow.[3] Cumulative urinary excretion during 16 days accounted for approximately 50% of the drug. The fecal route of excretion did not seem to be important.[3]

Protriptyline has uniquely low dosing among TCAs, likely due to its exceptionally long

terminal half-life.[18] It is used in dosages of 15 to 40 mg/day, whereas most other TCAs are used at dosages of 75 to 300 mg/day.[18] The maximum dose is 60 mg/day.[18] Therapeutic levels of protriptyline are typically in the range of 70 to 250 ng/mL (266-950 nmol/L), which is similar to that of other TCAs[19][20][21]

Chemistry

Protriptyline is a

molecular weight of 263.377 g/mol.[28] The drug is used commercially mostly as the hydrochloride salt; the free base form is not used.[28][29] The CAS Registry Number of the free base is 438-60-8 and of the hydrochloride is 1225-55-4.[28][29]

History

Protriptyline was developed by Merck.[30] It was patented in 1962 and first appeared in the literature in 1964.[30] The drug was first introduced for the treatment of depression in 1966.[30][31]

Society and culture

Generic names

Protriptyline is the

Latin is protriptylinum.[29][33]

Brand names

Protriptyline is or has been marketed throughout the world under a variety of brand names including Anelun, Concordin, Maximed, Triptil, and Vivactil.[28][29]

Availability

The sale of protriptyline was discontinued in the United Kingdom, Australia, and Ireland in 2000.[34]

See also

References

  1. ^ Anvisa (2023-03-31). "RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial" [Collegiate Board Resolution No. 784 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control] (in Brazilian Portuguese). Diário Oficial da União (published 2023-04-04). Archived from the original on 2023-08-03. Retrieved 2023-08-16.
  2. ^
    ISBN 978-1-60913-345-0
    .
  3. ^ a b c d e f g h i j k l m n o p q r s t u DURAMED PHARMACEUTICALS, INC., . (Ed.). (2007). Protriptyline drug facts. Pomona, New York : Barr Pharmaceuticals, Inc.
  4. ^ ULTRAM, . (Ed.). (2007). Protriptyline. Ortho-McNeil Pharmaceutical Inc.
  5. ^ a b c d e f g h i j k l m n o p q r s t u v w American Society of Health-System Pharmacists. AHFS Drug Information 2002. Bethesda: American Society of Health-System Pharmacists, 2002.
  6. ^
    PMID 15037866
    .
  7. ^ a b c d e f g Advameg, Inc. (2010). Protriptyline at MindDisorders.com
  8. ^ 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.
  9. PMID 2393207
    .
  10. ^ Roth BL, Driscol J. "PDSP Ki Database". Psychoactive Drug Screening Program (PDSP). University of North Carolina at Chapel Hill and the United States National Institute of Mental Health. Retrieved 7 May 2022.
  11. ^
    PMID 9537821
    .
  12. ^
    PMID 3816971
    .
  13. ^
    PMID 6086881
    .
  14. PMID 8699
    .
  15. ^
    S2CID 14274150
    .
  16. PMID 6297650
    .
  17. ^ "PDSP Database - UNC". PDSP Ki Database. University of North Carolina. Retrieved 15 July 2017.
  18. ^
    ISBN 978-1-108-22874-9
    .
  19. ISBN 978-0-8036-5845-5
    .
  20. ISBN 978-0-87630-964-3
    .
  21. ISBN 978-1-58562-309-9
    .
  22. ^
    ISBN 978-94-007-5805-6
    .
  23. ISBN 978-0-7817-6879-5
    .
  24. ISBN 978-0-471-95052-3
    .
  25. ISBN 978-3-527-64632-6
    .
  26. ISBN 978-1-56053-470-9
    .
  27. ISBN 978-0-19-162675-3
    .
  28. ^
    ISBN 978-1-4757-2085-3
    .
  29. ^
    ISBN 978-3-88763-075-1
    .
  30. ^
    PMID 19557250
    .
  31. ISBN 978-0-7817-2845-4
    .
  32. ISBN 978-94-011-4439-1
    .
  33. ^ a b "Protriptyline Uses, Side Effects & Warnings".
  34. ^ "Protriptyline". www.choiceandmedication.org. Archived from the original on 2012-11-22.