Cyproheptadine
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| 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 |
| Pregnancy cat. | B (US) |
| Legal status | P (UK) |
| Routes | Oral |
| Pharmacokinetic data | |
| Protein binding | 96 to 99% |
| Metabolism | Hepatic and renal |
| Half-life | 8.6 hours[1] |
| Excretion | Fecal and renal |
| Identifiers | |
| CAS number | 129-03-3  969-33-5 (hydrochloride) |
| ATC code | R06AX02 |
| PubChem | CID 2913 |
| IUPHAR ligand | 277 |
| DrugBank | DB00434 |
| ChemSpider | 2810 |
| UNII | 2YHB6175DO |
| KEGG | D07765 |
| ChEBI | CHEBI:4046 |
| ChEMBL | CHEMBL516 |
| Chemical data | |
| Formula | C21H21N |
| Mol. mass | 287.398 g/mol |
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Cyproheptadine (
/ˌsaɪprɵˈhɛptədiːn/), sold under the brand name Periactin, is a first-generation antihistamine with additional anticholinergic, antiserotonergic, and local anesthetic properties.
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[edit] Indications
- Has shown effectiveness in the treatment of nightmares including nightmares related to post traumatic stress disorder.[3][4]
- 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, such as selective serotonin reuptake inhibitors and monoamine oxidase inhibitors),[5][6][7] and in cases of hyperserotoninaemia resulting from a serotonin producing carcinoid tumour [8][9]
- Can also be used as a preventive measure against migraine in children and adolescents.[10][11][12][13][14]
- Can relieve SSRI-induced sexual dysfunction[15][16] and drug-induced hyperhidrosis (excessive sweating).[17]
- Also used in the treatment of cyclical vomiting syndrome[18] and to stimulate the appetite.[19]
- According to a small study, cyproheptadine hydrochloride has been found to improve sleep, calmness and negative symptoms in chronic schizophrenics who do not respond to other therapies.[20]
[edit] Pharmacology
Cyproheptadine is known to be an antagonist (or inverse agonist depending on the site in question) of the following receptors, listed in order of potency from greatest to least (Ki):
- H1 (~0.05 nM)[21] > 5-HT2A (~2 nM)[22] ≈ 5-HT2B (~1.5 nM)[23] ≈ 5-HT2C (~2 nM)[23] > mACh (M1-M5; ~7-12 nM)[24] ≈ D3 (~8 nM)[25]
It also has weak but likely negligible affinity for the following sites (Ki):
- 5-HT1A (~60-100 nM)[22][25] ≈ α1-adrenergic (?? nM)[26] ≈ α2-adrenergic (?? nM)[26] > 5-HT6 (~135-150 nM)[27][28] ≈ 5-HT7 (~125 nM)[28] ≈ D1 (~115 nM)[25] ≈ D2 (~115 nM)[25] > 5-HT3 (~250 nM)[25][29] ≈ NET (~300 nM)[30]
Additionally, cyproheptadine possesses calcium channel-blocking[31] and local anesthetic properties.[32]
[edit] Pharmacokinetics
Cyproheptadine is well-absorbed following oral ingestion, with peak plasma levels occurring after 1-3 hours.[33] Its half-life when taken orally is approximately 8 hours.[1]
[edit] Adverse effects
While not specifically used as a sedative, cyproheptadine causes drowsiness,[34] as is common with first-generation antihistamines.
Research has shown a suppression of growth hormone with doses of 8–12 mg per day taken for 5 days.[35]
Other common side effects include:[36]
- Dizziness
- Blurred vision
- Constipation
- Dry mouth, throat, or nose
- Excitability
- Nausea
- Nervousness
- Restlessness
[edit] Veterinary use
Cyproheptadine is used in cats as an appetite stimulant and as an adjunct in the treatment of asthma.[37][38] Possible adverse effects include excitement and aggressive behavior.[37] The elimination half-life of cyproheptadine in cats is 12 hours.[38]
Cyproheptadine has been used successfully in treatment of Pituitary Pars Intermedia Dysfunction (PPID) in horses. [39]
[edit] References
- ^ 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. PMID 15083941.
- ^ MedlinePlus Drug Information: Cyproheptadine
- ^ 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. http://ajp.psychiatryonline.org/cgi/content/full/157/9/1524-a.
- ^ 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.
- ^ Mills KC (October 1995). "Serotonin syndrome". American Family Physician 52 (5): 1475–82. PMID 7572570.
- ^ Gillman PK (1999). "The serotonin syndrome and its treatment". Journal of Psychopharmacology (Oxford, England) 13 (1): 100–9. doi:10.1177/026988119901300111. PMID 10221364.
- ^ Hall M, Buckley N (2003). "Serotonin syndrome". Australian Prescriber 26 (3): 62–3. http://www.australianprescriber.com/magazine/26/3/62/3.
- ^ 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. http://gut.bmj.com/cgi/pmidlookup?view=long&pmid=4274414.
- ^ 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. http://www3.interscience.wiley.com/journal/112674381/abstract.
- ^ Wendy G Mitchell et al. (2006). "Childhood Migraine Variants". http://www.emedicine.com/neuro/TOPIC494.HTM.
- ^ UVA Neurogram: Treatment of Pediatric Migraine
- ^ Netdoctor: Periactin
- ^ Migraines in Children and Adolescents
- ^ Klimek A (1979). "Cyproheptadine (Peritol) in the treatment of migraine and related headache". Ther Hung 27 (2): 93–4. PMID 494146.
- ^ 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.
- ^ 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.
- ^ 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. http://ajp.psychiatryonline.org/cgi/pmidlookup?view=long&pmid=11986151.
- ^ 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. http://pediatrics.aappublications.org/cgi/content/abstract/100/6/977.
- ^ Long-term trial of cyproheptadine as an appetite stimulant in cystic fibrosis | Wiley Online Library
- ^ "Cyproheptadine, Human Health Effects". Toxicology Data Network. 2003. http://toxnet.nlm.nih.gov/cgi-bin/sis/search/a?dbs+hsdb:@term+@DOCNO+3048. Retrieved 8 November 2012.
- ^ Moguilevsky N, Varsalona F, Noyer M, et al. (September 1994). "Stable expression of human H1-histamine-receptor cDNA in Chinese hamster ovary cells. Pharmacological characterisation of the protein, tissue distribution of messenger RNA and chromosomal localisation of the gene". European Journal of Biochemistry / FEBS 224 (2): 489–95. doi:10.1111/j.1432-1033.1994.00489.x. PMID 7925364. http://onlinelibrary.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0014-2956&date=1994&volume=224&issue=2&spage=489.
- ^ a b Peroutka SJ (May 1988). "Antimigraine drug interactions with serotonin receptor subtypes in human brain". Annals of Neurology 23 (5): 500–4. doi:10.1002/ana.410230512. PMID 2898916.
- ^ a b Bonhaus DW, Weinhardt KK, Taylor M, et al. (1997). "RS-102221: a novel high affinity and selective, 5-HT2C receptor antagonist". Neuropharmacology 36 (4–5): 621–9. doi:10.1016/S0028-3908(97)00049-X. PMID 9225287.
- ^ Stanton T, Bolden-Watson C, Cusack B, Richelson E (June 1993). "Antagonism of the five cloned human muscarinic cholinergic receptors expressed in CHO-K1 cells by antidepressants and antihistaminics". Biochemical Pharmacology 45 (11): 2352–4. doi:10.1016/0006-2952(93)90211-E. PMID 8100134.
- ^ a b c d e Toll L, Berzetei-Gurske IP, Polgar WE, et al. (March 1998). "Standard binding and functional assays related to medications development division testing for potential cocaine and opiate narcotic treatment medications". NIDA Research Monograph 178: 440–66. PMID 9686407.
- ^ a b F. S. Dukhovich (15 August 2005). Pharmacological aspects of molecular recognition. Nova Publishers. p. 117. ISBN 978-1-59454-676-1. http://books.google.com/books?id=9hvuXVPepMQC&pg=PA117. Retrieved 27 November 2011.
- ^ Kohen R, Metcalf MA, Khan N, et al. (January 1996). "Cloning, characterization, and chromosomal localization of a human 5-HT6 serotonin receptor". Journal of Neurochemistry 66 (1): 47–56. doi:10.1046/j.1471-4159.1996.66010047.x. PMID 8522988. http://onlinelibrary.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0022-3042&date=1996&volume=66&issue=1&spage=47.
- ^ a b Bard JA, Zgombick J, Adham N, Vaysse P, Branchek TA, Weinshank RL (November 1993). "Cloning of a novel human serotonin receptor (5-HT7) positively linked to adenylate cyclase". The Journal of Biological Chemistry 268 (31): 23422–6. PMID 8226867. http://www.jbc.org/cgi/pmidlookup?view=long&pmid=8226867.
- ^ Hoyer D, Neijt HC (March 1988). "Identification of serotonin 5-HT3 recognition sites in membranes of N1E-115 neuroblastoma cells by radioligand binding". Molecular Pharmacology 33 (3): 303–9. PMID 3352595. http://molpharm.aspetjournals.org/cgi/pmidlookup?view=long&pmid=3352595.
- ^ Runyon SP, Savage JE, Taroua M, Roth BL, Glennon RA, Westkaemper RB (March 2001). "Influence of chain length and N-alkylation on the selective serotonin receptor ligand 9-(aminomethyl)-9,10-dihydroanthracene". Bioorganic & Medicinal Chemistry Letters 11 (5): 655–8. doi:10.1016/S0960-894X(01)00023-3. PMID 11266163. http://linkinghub.elsevier.com/retrieve/pii/S0960894X01000233.
- ^ Lowe DA, Matthews EK, Richardson BP (November 1981). "The calcium antagonistic effects of cyproheptadine on contraction, membrane electrical events and calcium influx in the guinea-pig taenia coli". British Journal of Pharmacology 74 (3): 651–63. PMC 2071752. PMID 6271323. //www.ncbi.nlm.nih.gov/pmc/articles/PMC2071752/.
- ^ Riccioppo Neto F (March 1979). "The local anesthetic effect of cyproheptadine on mammalian nerve fibres". European Journal of Pharmacology 54 (3): 203–7. doi:10.1016/0014-2999(79)90078-5. PMID 428422.
- ^ Lindsay Murray; Frank Daly; David McCoubrie; Mike Cadogan (15 January 2011). Toxicology Handbook. Elsevier Australia. p. 388. ISBN 978-0-7295-3939-5. http://books.google.com/books?id=KDOeIldGWxQC&pg=PT388. Retrieved 27 November 2011.
- ^ Lexi-Comp (August 2008). "Cyproheptadine". The Merck Manual Professional. http://www.merck.com/mmpe/lexicomp/cyproheptadine.html. Retrieved on October 26, 2008.
- ^ 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.
- ^ Cyproheptadine - Drugs.com
- ^ 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. http://www.merckvetmanual.com/mvm/index.jsp?cfile=htm/bc/190302.htm. Retrieved on October 26, 2008.
- ^ 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. http://www.merckvetmanual.com/mvm/index.jsp?cfile=htm/bc/190907.htm. Retrieved on October 26, 2008.
- ^ Merck Vet Manual. "Hirsutism Associated with Adenomas of the Pars Intermedia". http://www.merckvetmanual.com/mvm/index.jsp?cfile=htm/bc/40504.htm. Retrieved April 24, 2011.
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