Systematic (IUPAC) name
4-(5H-dibenzo [a,d]cyclohepten-5-ylidene)-1-methylpiperidine hydrochloride
Clinical data
Trade names Periactin
Licence data US Daily Med:
  • AU: A
  • US: B (No risk in non-human studies)
Legal status
Routes of
Pharmacokinetic data
Protein binding 96 to 99%
Metabolism Hepatic[1][2]
Biological half-life 8.6 hours[3]
Excretion Faecal (2-20%; 34% of this as unchanged drug) and renal (40%; none as unchanged drug)[1][2]
CAS Registry Number  Y 969-33-5 (hydrochloride)
ATC code R06
PubChem CID:
DrugBank  Y
ChemSpider  Y
Chemical data
Formula C21H21N
Molecular mass 287.398 g/mol

Cyproheptadine , sold under the brand name Periactin or Peritol, is a first-generation antihistamine with additional anticholinergic, antiserotonergic, and local anesthetic properties.


  • Medical uses 1
  • Adverse effects 2
    • Overdose 2.1
  • Pharmacology 3
  • Pharmacokinetics 4
  • Veterinary use 5
  • See also 6
  • References 7

Medical uses

Periactin (cyproheptadine) 4 mg tablets
  • Cyproheptadine is used to treat allergic reactions (specifically hay fever).[4] It is also used to treat vasomotor mucosal edema, including vasomotor rhinitis and edema of the throat.
  • It has shown effectiveness in the treatment of nightmares, including those related to post-traumatic stress disorder.[5][6]
  • It has been used in the management of moderate to severe cases of serotonin syndrome, a complex of symptoms associated with the use of serotonergic drugs,[7] such as selective serotonin reuptake inhibitors and monoamine oxidase inhibitors),[8][9][10] and in cases of high levels of serotonin in the blood resulting from a serotonin-producing carcinoid tumor.[11][12]
  • It can also be used as a preventive measure against migraine in children and adolescents.[13][14][15][16][17] In Australia this is the only indication for which cyproheptadine is subsidised by the PBS.[7]
  • It can relieve SSRI-induced sexual dysfunction[18] and drug-induced hyperhidrosis (excessive sweating).[19]
  • It is also used in the treatment of cyclical vomiting syndrome[20]
  • Use of the drug can stimulate the appetite and may lead to weight gain, which is helpful for underweight people.[21]
  • According to a small study, cyproheptadine hydrochloride has been found to improve sleep, calmness, and mood and energy levels, and to improve both negative and (sometimes even) positive psychotic symptoms in a subgroup of chronic schizophrenics who did not respond (either completely or sufficiently) to other therapies.[22]
  • Cyproheptadine may improve akathisia in patients on antipsychotic medications.[23]
  • In clinical trials in which cyproheptadine was used as an adjunct to antipsychotic treatment for patients with schizophrenia, an improvement in negative symptoms was seen.[24]

Adverse effects

Adverse effects include[1][2]

  • 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
  • Diphoresis
  • 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:
- Hepatitis
- Jaundice
- Hepatic failure
- Hepatic function abnormality
- 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

Research has shown a suppression of growth hormone with doses of 8–12 mg per day taken for 5 days.[25]


Supportive measures such as gastric lavage or induced emesis are usually recommended in cases of overdose. The symptoms are usually indicative of CNS depression (or conversely CNS stimulation in some) and excess anticholinergic side effects. The LD50 in mice is 123 mg/kg and 295 mg/kg in rats.[1][2]


Cyproheptadine is known to be an antagonist (or inverse agonist depending on the site in question) of the receptors listed in the table below.

Receptor/Transporter Protein Binding affinity (Ki[nM]) towards cloned human receptors unless otherwise specified[26]
SERT 4100 (RC)
NET 290 (RC)
5-HT1A 59
5-HT2A 1.67
5-HT2B 1.54
5-HT2C 2.23
5-HT3 228 (MN)
5-HT6 142
5-HT7 123.01
M1 12
M2 7
M3 12
M4 8
M5 11.8
D1 117
D2 112
D3 8
H1 0.06
H3 >10000
H4 201.5

Acronyms used:
RC - Cloned rat receptor.
MN - Mouse NG108-15 receptor.


Cyproheptadine is well-absorbed following oral ingestion, with peak plasma levels occurring after 1–3 hours.[27] Its half-life when taken orally is approximately 8 hours.[3]

Veterinary use

Cyproheptadine is used in cats as an appetite stimulant and as an adjunct in the treatment of asthma.[28][29] Possible adverse effects include excitement and aggressive behavior.[28] The elimination half-life of cyproheptadine in cats is 12 hours.[29]

Cyproheptadine has been used successfully in treatment of pituitary pars intermedia dysfunction in horses.[30]

See also


  1. ^ a b c d "CYPROHEPTADINE HYDROCHLORIDE tablet [Boscogen, Inc.]" (PDF). DailyMed. Boscogen, Inc. November 2010. Retrieved 26 October 2013. 
  2. ^ a b c d "PRODUCT INFORMATION PERIACTIN® (cyproheptadine hydrochloride)" (PDF). Aspen Pharmacare Australia. Aspen Pharmacare Australia Pty Ltd. 17 November 2011. Retrieved 26 October 2013. 
  3. ^ a b Gunja N, Collins M, Graudins A (2004). "A comparison of the pharmacokinetics of oral and sublingual cyproheptadine". Journal of Toxicology. Clinical Toxicology 42 (1): 79–83.  
  4. ^ MedlinePlus Drug Information: Cyproheptadine
  5. ^ Rijnders, R. J.P.; Laman, DM; Van Diujn, H (2000). "Cyproheptadine for Posttraumatic Nightmares". American Journal of Psychiatry 157 (9): 1524–a.  
  6. ^ Gupta, S; Popli, A; Bathurst, E; Hennig, L; Droney, T; Keller, P (May 1998). "Efficacy of cyproheptadine for nightmares associated with posttraumatic stress disorder". Comprehensive Psychiatry 39 (3): 160–4.  
  7. ^ a b Rossi, S, ed. (2013). Australian Medicines Handbook (2013 ed.). Adelaide: The Australian Medicines Handbook Unit Trust.  
  8. ^ Mills KC (October 1995). "Serotonin syndrome". American Family Physician 52 (5): 1475–82.  
  9. ^ Gillman PK (1999). "The serotonin syndrome and its treatment". Journal of Psychopharmacology (Oxford, England) 13 (1): 100–9.  
  10. ^ Hall M, Buckley N (2003). "Serotonin syndrome". Australian Prescriber 26 (3): 62–3. 
  11. ^ Berry EM, Maunder C, Wilson M (January 1974). "Carcinoid myopathy and treatment with cyproheptadine (Periactin)". Gut 15 (1): 34–8.  
  12. ^ Moertel, Charles G.; Kvols, LK; Rubin, J (1991). "A study of cyproheptadine in the treatment of metastatic carcinoid tumor and the malignant carcinoid syndrome". Cancer 67 (1): 33–6.  
  13. ^ Wendy G Mitchell; et al. (2006). "Childhood Migraine Variants". 
  14. ^ UVA Neurogram: Treatment of Pediatric Migraine
  15. ^ Netdoctor: Periactin
  16. ^ Migraines in Children and Adolescents
  17. ^ Klimek A (1979). "Cyproheptadine (Peritol) in the treatment of migraine and related headache". Ther Hung 27 (2): 93–4.  
  18. ^ Cohen AJ (June 1992). "Fluoxetine induced yawning and anorgasmia reversed by cyproheptadine treatment".  
  19. ^ Ashton AK, Weinstein WL (May 2002). "Cyproheptadine for drug-induced sweating".  
  20. ^ Andersen JM, Sugerman KS, Lockhart JR, Weinberg WA (December 1997). "Effective Prophylactic Therapy for Cyclic Vomiting Syndrome in Children Using Amitriptyline or Cyproheptadine".  
  21. ^ Long-term trial of cyproheptadine as an appetite stimulant in cystic fibrosis | Wiley Online Library
  22. ^ "Cyproheptadine, Human Health Effects". Toxicology Data Network. 2003. Retrieved 8 November 2012. 
  23. ^ Taylor, D; Paton, C; Shitij, K (2012). Maudsley Prescribing Guidelines in Psychiatry (11th ed.). West Sussex: Wiley-Blackwell.  
  24. ^ Silver, H; Blacker, M; Weller, MPI; Lerer, B (February 1989). "Treatment of chronic schizophrenia with cyproheptadine". Biological Psychiatry 25 (4).  
  25. ^ Rosskamp RH, Haverkamp F, von Kalckreuth G (May 1990). "The effect of cyproheptadine on plasma growth hormone (GH) and on somatostatin response to GH-releasing hormone in man". Horm. Metab. Res. 22 (5): 295–7.  
  26. ^ Roth BL, Driscol J (12 January 2011). Database"i"PDSP K. Psychoactive Drug Screening Program (PDSP). University of North Carolina at Chapel Hill and the United States National Institute of Mental Health. Retrieved 26 October 2013. 
  27. ^ Lindsay Murray; Frank Daly; David McCoubrie; Mike Cadogan (15 January 2011). Toxicology Handbook. Elsevier Australia. p. 388.  
  28. ^ a b Dowling PM (February 8, 2005). "Drugs Affecting Appetite". In Kahn CM, Line S, Aiello SE (eds.).   Retrieved on October 26, 2008.
  29. ^ a b Dowling PM (February 8, 2005). "Systemic Therapy of Airway Disease: Cyproheptadine". In Kahn CM, Line S, Aiello SE (eds.). The Merck Veterinary Manual (9th ed.).   Retrieved on October 26, 2008.
  30. ^ Merck Vet Manual. "Hirsutism Associated with Adenomas of the Pars Intermedia". Retrieved April 24, 2011.