Cyproheptadine

Source: Wikipedia, the free encyclopedia.

Cyproheptadine
Clinical data
Pronunciation/ˌsaɪproʊˈhɛptədiːn/[1]
Trade namesPeriactin, others
AHFS/Drugs.comMonograph
MedlinePlusa682541
License data
Pregnancy
category
  • AU: A
Routes of
administration		Oral
ATC code
Legal status
Legal status
renal (40%; none as unchanged drug)[3][4]
Identifiers
  • 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-methylpiperidine
JSmol)
  • c43\C(=C1/CCN(C)CC1)c2ccccc2\C=C/c3cccc4
  • InChI=1S/C21H21N/c1-22-14-12-18(13-15-22)21-19-8-4-2-6-16(19)10-11-17-7-3-5-9-20(17)21/h2-11H,12-15H2,1H3 checkY
  • Key:JJCFRYNCJDLXIK-UHFFFAOYSA-N checkY
  (verify)

Cyproheptadine, sold under the brand name Periactin among others, is a

antiserotonergic, and local anesthetic
properties.

It was patented in 1959 and came into medical use in 1961.[5] In 2021, it was the 280th most commonly prescribed medication in the United States, with more than 800,000 prescriptions.[6][7]

Medical uses

Periactin (cyproheptadine) 4 mg tablets
Cyproheptadine's 3D molecular structure represented as space-filling model

Cyproheptadine is used to treat allergic reactions (specifically

hay fever).[8] The evidence for its use for this purpose indicates its effectiveness but second generation antihistamines such as ketotifen and loratadine have shown equal results with fewer side effects.[9]

It is also used as a preventive treatment against migraine. In a 2013 study the frequency of migraine was dramatically reduced in patients within 7 to 10 days after starting treatment. The average frequency of migraine attacks in these patients before administration was 8.7 times per month, this was decreased to 3.1 times per month at 3 months after the start of treatment.[9][10] This use is on the label in the UK and some other countries.

It is also used off-label in the treatment of

cyclical vomiting syndrome in infants; the only evidence for this use comes from retrospective studies.[11]

Cyproheptadine is sometimes used off-label to improve akathisia in people on antipsychotic medications.[12]

It is used off-label to treat various dermatological conditions, including psychogenic itch[13] drug-induced hyperhidrosis (excessive sweating),[14] and prevention of blister formation for some people with epidermolysis bullosa simplex.[15]

One of the effects of the drug is increased appetite and weight gain, which has led to its use (off-label in the USA) for this purpose in children who are wasting as well as people with cystic fibrosis.[16][17][18][19]

It is also used off-label in the management of moderate to severe cases of

monoamine oxidase inhibitors), and in cases of high levels of serotonin in the blood resulting from a serotonin-producing carcinoid tumor.[20][21]

Cyproheptadine has sedative effects and can be used to treat insomnia similarly to other centrally-acting antihistamines.[22][23][24][25] The recommended dose for this use is 4 to 8 mg.[23]

Adverse effects

Adverse effects include:[3][4]

  • Sedation and sleepiness (often transient)
  • Dizziness
  • Disturbed coordination
  • Confusion
  • Restlessness
  • Excitation
  • Nervousness
  • Tremor
  • Irritability
  • Insomnia
  • Paresthesias
  • Neuritis
  • Convulsions
  • Euphoria
  • Hallucinations
  • Hysteria
  • Faintness
  • Allergic manifestation of rash and edema
  • Diaphoresis
  • Urticaria
  • Photosensitivity
  • Acute labyrinthitis
  • Diplopia (seeing double)
  • Vertigo
  • Tinnitus
  • Hypotension (low blood pressure)
  • Palpitation
  • Extrasystoles
  • Anaphylactic shock
  • Hemolytic anemia
  • Blood dyscrasias such as leukopenia, agranulocytosis and thrombocytopenia
  • Cholestasis
  • Hepatic (liver) side effects such as:
  • Epigastric
    distress
  • Anorexia
  • Nausea
  • Vomiting
  • Diarrhea
  • Anticholinergic side effects such as:
    • Blurred vision
    • Constipation
    • Xerostomia (dry mouth)
    • Tachycardia (high heart rate)
    • Urinary retention
    • Difficulty passing urine
    • Nasal congestion
    • Nasal or throat dryness
  • Urinary frequency
  • Early menses
  • Thickening of bronchial secretions
  • Tightness of chest and wheezing
  • Fatigue
  • Chills
  • Headache
  • Increased appetite
  • Weight gain

Overdose

Gastric decontamination measures such as

LD50 in mice is 123 mg/kg and 295 mg/kg in rats.[3][4]

Pharmacology

Pharmacodynamics

Cyproheptadine[27]
Site Ki (nM)[a] Action[b] Species Ref.
H1 0.06 ↓ Human
H2 ND ND
H3 >10,000 Human
H4 202 Human
M1 12 ↓ Human
M2 7 ↓ Human
M3 12 ↓ Human
M4 8 ↓ Human
M5 11.8 ↓ Human
5-HT1A 59 ↓ Human
5-HT2A 1.67 ↓ Human
5-HT2B 1.54 ↓ Human
5-HT2C 2.23 ↓ Human
5-HT3 228 Mouse
5-HT6 142 Human
5-HT7 123 Human
D1
 117 Human
D2
 112 ↓ Human
D3
 8 Human
SERTTooltip Serotonin transporter 4,100 Rat
NETTooltip Norepinephrine transporter 290 Rat
DATTooltip Dopamine transporter ND ND
  1. ^ The smaller the equilibrium constant, the more strongly the drug binds to the site.
  2. ^
    • ↑ Agonist
    • ↓ Antagonist

Cyproheptadine is a very potent

serotonin receptors, it is an especially potent antagonist of the 5-HT2 receptors. This is thought to underlie its effectiveness in the treatment of serotonin syndrome.[28] However, it is possible that blockade of 5-HT1 receptors may also contribute to its effectiveness in serotonin syndrome.[29] Cyproheptadine has been reported to block 85% of 5-HT2 receptors in the human brain at a dose of 4 mg three times per day (12 mg/day total) and to block 95% of 5-HT2 receptors in the human brain at a dose of 6 mg three times per day (18 mg/day total) as measured with positron emission tomography (PET).[30] The dose of cyproheptadine recommended to ensure blockade of the 5-HT2 receptors for serotonin syndrome is 20 to 30 mg.[28] Besides its activity at neurotransmitter targets, cyproheptadine has been reported to possess weak antiandrogenic activity.[31]

Pharmacokinetics

Cyproheptadine is well-absorbed following

terminal half-life when taken orally is approximately 8 hours.[2]

Chemistry

Cyproheptadine is a tricyclic benzocycloheptene and is closely related to pizotifen and ketotifen as well as to tricyclic antidepressants.

Research

Cyproheptadine was studied in one small trial as an adjunct in people with schizophrenia whose condition was stable and were on other medication; while attention and verbal fluency appeared to be improved, the study was too small to draw generalizations from.[33] It has also been studied as an adjuvant in two other trials in people with schizophrenia, around fifty people overall, and did not appear to have an effect.[34]

There have been some trials to see if cyproheptadine could reduce sexual dysfunction caused by SSRI and antipsychotic medications.[35]

Cyproheptadine has been studied for the treatment of post-traumatic stress disorder.[34]

Veterinary use

Cyproheptadine is used in cats as an

elimination half-life of cyproheptadine in cats is 12 hours.[38]

Cyproheptadine is a second line treatment for pituitary pars intermedia dysfunction in horses.[40][41]

References

  1. ^ "Cyproheptadine". Dictionary.com Unabridged (Online). n.d.
  2. ^
    S2CID 20196551
    .
  3. ^ a b c d "Cyproheptadine Hydrochloride tablet [Boscogen, Inc.]" (PDF). DailyMed. U.S. National Library of Medicine. November 2010. Retrieved 26 October 2013.
  4. ^ a b c d "Product Information: Periactin (cyproheptadine hydrochloride)" (PDF). Aspen Pharmacare Australia. Aspen Pharmacare Australia Pty Ltd. 17 November 2011. Archived from the original (PDF) on 29 October 2013. Retrieved 26 October 2013.
  5. ISBN 9783527607495
    .
  6. ^ "The Top 300 of 2021". ClinCalc. Archived from the original on 15 January 2024. Retrieved 14 January 2024.
  7. ^ "Cyproheptadine - Drug Usage Statistics". ClinCalc. Retrieved 14 January 2024.
  8. ^ "Cyproheptadine". MedlinePlus Drug Information. U.S. National Library of Medicine.
  9. ^
    S2CID 21185048
    .
  10. S2CID 34703034
    .
  11. PMID 27423188
    .
  12. ISBN 978-1-118-75457-3
    .
  13. PMID 27578081
    .
  14. PMID 11986151
    .
  15. PMID 20301543
    .
  16. ^ "Ciproheptadina, estimulante del apetito" [Cyproheptadine, appetite stimulant]. vademecum.es (in Spanish).
  17. ^ "Bioplex NF". Archived from the original on 18 April 2018. Retrieved 18 April 2018.
  18. S2CID 72333631
    .
  19. S2CID 237493456
    .
  20. ISBN 978-0-9805790-9-3
    .
  21. PMID 23145389
    .
  22. PMID 33632345
    .
  23. ^
    S2CID 227131545
    .
  24. ProQuest 301570569
    .
  25. PMID 334082
    .
  26. PMID 25580444
    .
  27. ^ 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 14 August 2017.
  28. ^
    S2CID 17640246
    .
  29. S2CID 19809259
    .
  30. PMID 9167527
    .
  31. PMID 9476091
    .
  32. ISBN 978-0-7295-3939-5
    . Retrieved 27 November 2011.
  33. S2CID 19202816
    .
  34. ^
    S2CID 25769557
    .
  35. S2CID 23406005
    .
  36. S2CID 37126352
    .
  37. OCLC 794491298
    .
  38. ^
    ISBN 978-0-911910-50-6
    . Retrieved on 26 October 2008.
  39. ISBN 978-0-911910-50-6
    . Retrieved on 26 October 2008.
  40. PMID 28190613
    .
  41. ^ Kritchevsky JE (July 2019). "Hirsutism Associated with Adenomas of the Pars Intermedia". Merck Vet Manual. Retrieved 24 April 2011.