Cyproheptadine

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Cyproheptadine
Cyproheptadine.svg
Cyproheptadine3Dan.gif
Systematic (IUPAC) name
4-(5H-dibenzo [a,d]cyclohepten-5-ylidene)-1-methylpiperidine hydrochloride
Clinical data
Trade names Periactin
AHFS/Drugs.com monograph
MedlinePlus a682541
Licence data US Daily Med:link
Pregnancy cat. A (AU) B (US)
Legal status Pharmacist Only (S3) (AU) POM (UK)
Routes Oral
Pharmacokinetic data
Protein binding 96 to 99%
Metabolism Hepatic[1][2]
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]
Identifiers
CAS number 129-03-3 YesY 969-33-5 (hydrochloride)
ATC code R06AX02
PubChem CID 2913
IUPHAR ligand 277
DrugBank DB00434
ChemSpider 2810 YesY
UNII 2YHB6175DO YesY
KEGG D07765 YesY
ChEBI CHEBI:4046 YesY
ChEMBL CHEMBL516 YesY
Chemical data
Formula C21H21N 
Mol. mass 287.398 g/mol
 YesY (what is this?)  (verify)

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

Medical uses[edit]

Periactin (cyproheptadine) 4 mg tablets

Adverse effects[edit]

Adverse effects include[1][2]

  • Sedation and sleepiness (often transient)
  • Dizziness
  • Disturbed coordination
  • Confusion
  • Restlessness
  • Excitation
  • Nervousness
  • Tremor
  • Irritability
  • Insomnia
  • Paraesthesias
  • Neuritis
  • Convulsions
  • Euphoria
  • Hallucinations
  • Hysteria
  • Faintness
  • Allergic manifestation of rash and oedema
  • Diphoresis
  • Urticaria
  • Photosensitivity
  • Acute labyrinthitis
  • Diplopia (seeing double)
  • Vertigo
  • Tinnitus
  • Hypotension (low blood pressure)
  • Palpitation
  • Extrasystoles
  • Anaphylactic shock
  • Haemolytic anemia
  • Blood dyscarsias such as leukopenia, agranulocytosis and thrombocytopaenia
  • 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.[26]

Overdose[edit]

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]

Pharmacology[edit]

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[27]
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.

Pharmacokinetics[edit]

Cyproheptadine is well-absorbed following oral ingestion, with peak plasma levels occurring after 1–3 hours.[28] Its half-life when taken orally is approximately 8 hours.[3]

Veterinary use[edit]

Cyproheptadine is used in cats as an appetite stimulant and as an adjunct in the treatment of asthma.[29][30] Possible adverse effects include excitement and aggressive behavior.[29] The elimination half-life of cyproheptadine in cats is 12 hours.[30]

Cyproheptadine has been used successfully in treatment of Pituitary Pars Intermedia Dysfunction (PPID) in horses.[31]

Synthesis[edit]

Cyproheptadine synthesis:[32] U.S. Patent 3,014,911 Edward L Engelhardt; Merck & Co Inc. (1961)

Cyproheptadine is made from Dibenzosuberenone starting material (c.f. Cyclobenzaprine and also Zosuquidar)

See also[edit]

References[edit]

  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)". 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. doi:10.1081/clt-120028749. PMID 15083941. 
  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. doi:10.1176/appi.ajp.157.9.1524-a. PMID 10964879. 
  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. doi:10.1016/S0010-440X(98)90076-1. ISSN 0010-440X. PMID 9606583. 
  7. ^ a b Rossi, S, ed. (2013). Australian Medicines Handbook (2013 ed.). Adelaide: The Australian Medicines Handbook Unit Trust. ISBN 978-0-9805790-9-3.  edit
  8. ^ Mills KC (October 1995). "Serotonin syndrome". American Family Physician 52 (5): 1475–82. PMID 7572570. 
  9. ^ Gillman PK (1999). "The serotonin syndrome and its treatment". Journal of Psychopharmacology (Oxford, England) 13 (1): 100–9. doi:10.1177/026988119901300111. PMID 10221364. 
  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. doi:10.1136/gut.15.1.34. PMC 1412931. PMID 4274414. 
  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. doi:10.1002/1097-0142(19910101)67:1<33::AID-CNCR2820670107>3.0.CO;2-E. PMID 1985720. 
  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. PMID 494146. 
  18. ^ Keller Ashton A, Hamer R, Rosen RC (1997). "Serotonin reuptake inhibitor-induced sexual dysfunction and its treatment: a large-scale retrospective study of 596 psychiatric outpatients". Journal of Sex & Marital Therapy 23 (3): 165–75. doi:10.1080/00926239708403922. PMID 9292832. 
  19. ^ McCormick S, Olin J, Brotman AW (September 1990). "Reversal of fluoxetine-induced anorgasmia by cyproheptadine in two patients". Journal of Clinical Psychiatry 51 (9): 383–4. PMID 2211550. 
  20. ^ Ashton AK, Weinstein WL (May 2002). "Cyproheptadine for drug-induced sweating". American Journal of Psychiatry 159 (5): 874–5. doi:10.1176/appi.ajp.159.5.874-a. PMID 11986151. 
  21. ^ Andersen JM, Sugerman KS, Lockhart JR, Weinberg WA (December 1997). "Effective Prophylactic Therapy for Cyclic Vomiting Syndrome in Children Using Amitriptyline or Cyproheptadine". Pediatrics 100 (6): 977–981. doi:10.1542/peds.100.6.977. PMID 9374568. 
  22. ^ Long-term trial of cyproheptadine as an appetite stimulant in cystic fibrosis | Wiley Online Library
  23. ^ "Cyproheptadine, Human Health Effects". Toxicology Data Network. 2003. Retrieved 8 November 2012. 
  24. ^ Taylor, D; Paton, C; Shitij, K (2012). Maudsley Prescribing Guidelines in Psychiatry (in English) (11th ed.). West Sussex: Wiley-Blackwell. p. 104, 605. ISBN 978-0-47-097948-8.  edit
  25. ^ Silver, H; Blacker, M; Weller, MPI; Lerer, B (February 1989). "Treatment of chronic schizophrenia with cyproheptadine". Biological Psychiatry 25 (4). doi:10.1016/0006-3223(89)90206-0. 
  26. ^ 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. doi:10.1055/s-2007-1004905. PMID 1971804. 
  27. ^ Roth BL, Driscol J (12 January 2011). "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 26 October 2013. 
  28. ^ Lindsay Murray; Frank Daly; David McCoubrie; Mike Cadogan (15 January 2011). Toxicology Handbook. Elsevier Australia. p. 388. ISBN 978-0-7295-3939-5. Retrieved 27 November 2011. 
  29. ^ a b Dowling PM (February 8, 2005). "Drugs Affecting Appetite". In Kahn CM, Line S, Aiello SE (eds.). The Merck Veterinary Manual (9th ed.). John Wiley & Sons. ISBN 0-911910-50-6.  Retrieved on October 26, 2008.
  30. ^ 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.). John Wiley & Sons. ISBN 0-911910-50-6.  Retrieved on October 26, 2008.
  31. ^ Merck Vet Manual. "Hirsutism Associated with Adenomas of the Pars Intermedia". Retrieved April 24, 2011. 
  32. ^ doi:10.1021/jm00330a022
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