Cyproheptadine

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Cyproheptadine
Cyproheptadine.svg
Cyproheptadine-Spartan-PM3-3D-balls.png
Clinical data
Pronunciation /ˌsaɪproʊˈhɛptədiːn/ [1]
Trade names Periactin, others
AHFS/Drugs.com Monograph
MedlinePlus a682541
License data
Pregnancy
category
  • AU:A
Routes of
administration 		Oral
ATC code
Legal status
Legal status
Pharmacokinetic data
Protein binding 96 to 99%
Metabolism Liver, including glucuronidation [2] [3]
Elimination half-life 8.6 hours [4]
Excretion Faecal (2–20%; of which, 34% as unchanged drug) and renal (40%; none as unchanged drug) [2] [3]
Identifiers
  • 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-methylpiperidine
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard 100.004.482 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C21H21N
Molar mass 287.406 g·mol−1
3D model (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 Yes check.svgY
  • Key:JJCFRYNCJDLXIK-UHFFFAOYSA-N Yes check.svgY
   (verify)

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

Contents

It was patented in 1959 and came into medical use in 1961. [5] In 2023, it was the 234th most commonly prescribed medication in the United States, with more than 1 million prescriptions. [6] [7]

Medical uses

Periactin (cyproheptadine) 4 mg tablets Periactin.jpg
Periactin (cyproheptadine) 4 mg tablets
Cyproheptadine's 3D molecular structure represented as space-filling model Cyproheptadine3Dan.gif
Cyproheptadine's 3D molecular structure represented as space-filling model

Cyproheptadine is used to treat allergic reactions (specifically hay fever). [8] There is evidence supporting its use for allergies, 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 serotonin syndrome, a complex of symptoms associated with the use of serotonergic drugs, such as selective serotonin reuptake inhibitors (and 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: [2] [3]

Overdose

Gastric decontamination measures such as activated charcoal are sometimes 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. [2] [3]

Interactions

Cyproheptadine, due to its serotonin 5-HT2A receptor antagonism, may be useful as a hallucinogen antidote against serotonergic psychedelics or as a so-called "trip killer". [27] The drug has been clinically studied in combination with the serotonergic psychedelic dimethyltryptamine (DMT). [28] [29] [30] In an early study, cyproheptadine partially blocked the hallucinogenic effects of DMT in 2 of 3 subjects. [31] [32] [30] [33] In a follow-up study, pretreatment with cyproheptadine in 5 subjects failed to reduce the psychoactive effects of DMT and instead was found to actually intensify its effects in some cases, although the duration of DMT seemed to be shortened. [28] [29] [30] Subsequently, Rick Strassman and colleagues studied cyproheptadine in combination with DMT in 8 subjects and found that the hallucinogenic effects of DMT were not magnified but were reduced. [34] However, owing to the pronounced sedative effects of cyproheptadine, it was difficult to tell how much of cyproheptadine's effect was due to antagonism of DMT versus simple general tranquilization. [34] Overall, the findings have been described as inconclusive and higher doses of cyproheptadine being precluded by the drug's sedative effects. [35] It is unclear that cyproheptadine achieves adequate serotonin 5-HT2A receptor occupancy at the assessed doses. [28] [29] Further complicating the picture, high doses of cyproheptadine have been reported to produce partial LSD-like discriminative stimulus effects in animals. [28] [29] [36]

Pharmacology

Pharmacodynamics

Activities of cyproheptadine
SiteKi (nM)Action
5-HT1A 50–59↓
5-HT1B 1,600?
5-HT1D 670?
5-HT1E 1,500?
5-HT2A 0.46–3.0↓
5-HT2B 1.5–2.6↓
5-HT2C 2.2–18↓
5-HT3 235?
5-HT4 ND?
5-HT5A 57?
5-HT6 96–150?
5-HT7 30–126?
D1 10–117?
D2 74–112↓
D3 8?
D4 120?
D5 60?
α1A 45?
α1B >10,000?
α2A 330?
α2B 220?
α2C 160?
β1 >10,000?
β2 >10,000?
H1 0.06–2.3↓
H2 4.8?
H3 >10,000?
H4 202–>10,000?
M1 12↓
M2 7↓
M3 12↓
M4 8↓
M5 11.8↓
I1 204?
σ1 >10,000 (gp)?
σ2 750 (rat)?
SERT Tooltip Serotonin transporter>10,000–
NET Tooltip Norepinephrine transporter290–2,550–
DAT Tooltip Dopamine transporter4,100–
Notes: The smaller the value, the more avidly the drug binds to the site. All proteins are human unless otherwise noted. ↑ = Agonist. ↓ = Antagonist. Refs: [37] [38] [39]

Cyproheptadine is a very potent antihistamine or inverse agonist of the H1 receptor. At higher concentrations, it also has anticholinergic, antiserotonergic, and antidopaminergic activities.

Of the 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. [40] However, it is possible that blockade of 5-HT1 receptors may also contribute to its effectiveness in serotonin syndrome. [41] 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). [42] The dose of cyproheptadine recommended to ensure blockade of the 5-HT2 receptors for serotonin syndrome is 20 to 30 mg. [40]

Blockade of the serotonin 5-HT2B receptor may be specifically involved in the antimigraine effects of cyproheptadine. [43]

Cyproheptadine has been found to partially block the discriminative stimulus properties of the psychedelic drug LSD in rodent drug discrimination tests. [44] [45] [46] It also antagonizes the discriminative stimulus properties of various other serotonergic agents, like 5-MeO-DMT, quipazine, fenfluramine, and 5-hydroxytryptophan (5-HTP). [47] In addition, cyproheptadine blocks the head-twitch response induced by LSD, 5-MeO-DMT, quipazine, and 5-HTP in rodents. [48] [49] However, high doses of cyproheptadine have been reported to produce partial LSD-like discriminative stimulus effects in rodents. [44] [28] [29] [36] [50] [51] [52] Possibly in relation to this, cyproheptadine has been said to sometimes be associated with hallucinations in humans. [28] [29] As an alternative possibility however, the partial generalization may instead be related to the highly non-selective nature of cyproheptadine and interactions at other neurotransmitter sites. [50]

Besides its activity at neurotransmitter targets, cyproheptadine has been reported to possess weak antiandrogenic activity. [53]

Pharmacokinetics

Cyproheptadine is well-absorbed following oral ingestion, with peak plasma levels occurring after 1 to 3 hours. [54] Its terminal half-life when taken orally is approximately 8 hours. [4]

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. [55] 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. [56]

There have been some trials to see if cyproheptadine could reduce sexual dysfunction caused by selective serotonin reuptake inhibitor (SSRI) and antipsychotic medications. [57]

Cyproheptadine has been studied for the treatment of post-traumatic stress disorder. [56]

Veterinary use

Cyproheptadine is used in cats as an appetite stimulant [58] [59] : 1371  and as an adjunct in the treatment of asthma. [60] Possible adverse effects include excitement and aggressive behavior. [61] The elimination half-life of cyproheptadine in cats is 12 hours. [60]

Cyproheptadine is a second line treatment for pituitary pars intermedia dysfunction in horses. [62] [63]

References

  1. ↑ "Cyproheptadine". Dictionary.com Unabridged (Online). n.d.
  2. 1 2 3 4 "Cyproheptadine Hydrochloride tablet [Boscogen, Inc.]" (PDF). DailyMed. U.S. National Library of Medicine. November 2010. Retrieved 26 October 2013.
  3. 1 2 3 4 "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.
  4. 1 2 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. S2CID   20196551.
  5. ↑ Fischer J, Ganellin CR (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 547. ISBN   978-3-527-60749-5.
  6. ↑ "The Top 300 of 2023". ClinCalc. Archived from the original on 12 August 2025. Retrieved 12 August 2025.
  7. ↑ "Cyproheptadine Drug Usage Statistics, United States, 2013 - 2023". ClinCalc. Retrieved 20 August 2025.
  8. ↑ "Cyproheptadine". MedlinePlus Drug Information. U.S. National Library of Medicine.
  9. 1 2 De Bruyne P, Christiaens T, Boussery K, Mehuys E, Van Winckel M (January 2017). "Are antihistamines effective in children? A review of the evidence". Archives of Disease in Childhood. 102 (1): 56–60. doi:10.1136/archdischild-2015-310416. PMID   27335428. S2CID   21185048.
  10. ↑ Saito Y, Yamanaka G, Shimomura H, Shiraishi K, Nakazawa T, Kato F, et al. (May 2017). "Reconsideration of the diagnosis and treatment of childhood migraine: A practical review of clinical experiences". Brain & Development. 39 (5): 386–394. doi:10.1016/j.braindev.2016.11.011. PMID   27993427. S2CID   34703034.
  11. ↑ Salvatore S, Barberi S, Borrelli O, Castellazzi A, Di Mauro D, Di Mauro G, et al. (July 2016). "Pharmacological interventions on early functional gastrointestinal disorders". Italian Journal of Pediatrics. 42 (1) 68. doi: 10.1186/s13052-016-0272-5 . PMC   4947301 . PMID   27423188.
  12. ↑ Taylor DM, Paton C, Kapur S (2015). The Maudsley Prescribing Guidelines in Psychiatry. John Wiley & Sons. p. 85. ISBN   978-1-118-75457-3.
  13. ↑ Szepietowski JC, Reszke R (2016). "Psychogenic Itch Management". Current Problems in Dermatology. 50: 124–132. doi:10.1159/000446055. ISBN   978-3-318-05888-8. PMID   27578081.
  14. ↑ Ashton AK, Weinstein WL (May 2002). "Cyproheptadine for drug-induced sweating". The American Journal of Psychiatry. 159 (5): 874–875. doi:10.1176/appi.ajp.159.5.874-a. PMID   11986151.
  15. ↑ So JY, Teng J (1993). "Epidermolysis Bullosa Simplex". In Adam MP, Everman DB, Mirzaa GM, Pagon RA, Wallace SE, Bean LJ, Gripp KW, Amemiya A (eds.). GeneReviews. University of Washington, Seattle. 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. ↑ Harrison ME, Norris ML, Robinson A, Spettigue W, Morrissey M, Isserlin L (June 2019). "Use of cyproheptadine to stimulate appetite and body weight gain: A systematic review". Appetite. 137: 62–72. doi:10.1016/j.appet.2019.02.012. PMID   30825493. S2CID   72333631.
  19. ↑ Kim SY, Yun JM, Lee JW, Cho YG, Cho KH, Park YG, et al. (October 2021). "Efficacy and Tolerability of Cyproheptadine in Poor Appetite: A Multicenter, Randomized, Double-blind, Placebo-controlled Study". Clinical Therapeutics. 43 (10): 1757–1772. doi:10.1016/j.clinthera.2021.08.001. PMID   34509304. S2CID   237493456.
  20. ↑ Rossi S, ed. (2013). Australian Medicines Handbook (2013 ed.). Adelaide: The Australian Medicines Handbook Unit Trust. ISBN   978-0-9805790-9-3.
  21. ↑ Iqbal MM, Basil MJ, Kaplan J, Iqbal MT (November 2012). "Overview of serotonin syndrome". Annals of Clinical Psychiatry. 24 (4): 310–318. doi:10.1177/104012371202400410. PMID   23145389.
  22. ↑ Badr B, Naguy A (October 2022). "Cyproheptadine: a psychopharmacological treasure trove?". CNS Spectrums. 27 (5): 533–535. doi: 10.1017/S1092852921000250 . PMID   33632345.
  23. 1 2 Ekambaram V, Owens J (January 2021). "Medications Used for Pediatric Insomnia". Child and Adolescent Psychiatric Clinics of North America. 30 (1): 85–99. doi:10.1016/j.chc.2020.09.001. PMID   33223070. S2CID   227131545.
  24. ↑ Rombaut NE (1995). Antihistamines and Sedation: Methods and Measures (Thesis). OCLC   59660401. ProQuest   301570569.
  25. ↑ Wanderer AA, St Pierre JP, Ellis EF (October 1977). "Primary acquired cold urticaria. Double-blind comparative study of treatment with cyproheptadine, chlorpheniramine, and placebo". Archives of Dermatology. 113 (10): 1375–1377. doi:10.1001/archderm.113.10.1375. PMID   334082.
  26. ↑ Chertoff J, Alam S, Clark V (July 2014). "Cyproheptadine-Induced Acute Liver Failure". ACG Case Reports Journal. 1 (4): 212–213. doi:10.14309/crj.2014.56. PMC   4286888 . PMID   25580444.
  27. ↑ Aghajanian GK (1994). "Serotonin and the Action of LSD in the Brain" . Psychiatric Annals. 24 (3): 137–141. doi:10.3928/0048-5713-19940301-09. As yet there are no FDA-approved selective 5-HT2 antagonists available for use clinically. There are a few classical 5-HT antagonists (eg, cyproheptadine), approved for other indications that may have effectiveness against the hallucinogens since they have antagonist activity at 5-HT2 receptors. However, side effects produced by actions at other receptors may limit their clinical utility.
  28. 1 2 3 4 5 6 Halberstadt AL, Nichols DE (1 January 2010). "CHAPTER 4.7 - Serotonin and Serotonin Receptors in Hallucinogen Action". Handbook of Behavioral Neuroscience. Vol. 21. Elsevier. pp. 621–636. doi:10.1016/s1569-7339(10)70103-x. ISBN   978-0-12-374634-4 . Retrieved 9 July 2025. Meltzer and colleagues (Tueting et al., 1992) examined whether the moderately selective 5-HT 2A/2C antagonist cyproheptadine and the D2 antagonist haloperidol could block the psychological effects induced by DMT in normal human volunteers. Neither drug effectively blocked the effects of DMT, and in some subjects the effects of DMT were actually intensified by pretreatment with cyproheptadine. The finding that cyproheptadine intensified the effects of DMT is intriguing in light of reports that high doses of cyproheptadine produce LSD-like behavioral effects in rats (Colpaert et al., 1982). Nonetheless, it is not clear that the dose of cyproheptadine used in the study (4 mg, p.o.) produces significant occupation of 5-HT2 sites.
  29. 1 2 3 4 5 6 Halberstadt AL, Nichols DE (1 January 2020). "Chapter 43 - Serotonin and serotonin receptors in hallucinogen action". Handbook of Behavioral Neuroscience. Vol. 31. Elsevier. pp. 843–863. doi:10.1016/b978-0-444-64125-0.00043-8. ISBN   978-0-444-64125-0 . Retrieved 9 July 2025. DMT. Meltzer and colleagues (Tueting, Metz, Rhoades, & Boutros, 1992) examined whether the moderately selective 5-HT2A/2C antagonist cyproheptadine and the D2 antagonist haloperidol could block the psychological effects induced by DMT in normal human volunteers. Neither drug effectively blocked the effects of DMT, and in some subjects the effects of DMT were actually intensified by pretreatment with cyproheptadine. The finding that cyproheptadine intensified the effects of DMT is intriguing in light of reports that high doses of cyproheptadine produce LSD-like behavioral effects in rats (Colpaert et al., 1982). Nonetheless, it is not clear that the dose of cyproheptadine used in the study (4 mg, p.o.) produces significant occupation of 5-HT2 sites.
  30. 1 2 3 Tueting PA, Metz J, Rhoades BK, Boutros NN (July 1992). "Pharmacologic challenge in ERP research". Ann N Y Acad Sci. 658 (1): 223–255. Bibcode:1992NYASA.658..223T. doi:10.1111/j.1749-6632.1992.tb22847.x. PMID   1497260.
  31. ↑ Nichols DE (February 2004). "Hallucinogens". Pharmacol Ther. 101 (2): 131–181. doi:10.1016/j.pharmthera.2003.11.002. PMID   14761703. The most compelling evidence that hallucinogens have agonist activity at 5-HT2A receptors was obtained from two clinical studies. The first study was not definitive, however, where the mixed 5-HT2A/2C antagonist cyproheptadine antagonized the subjective effects of DMT in some subjects (Meltzer et al., 1982). [...]
  32. ↑ Strassman RJ (March 1995). "Hallucinogenic Drugs in Psychiatric Research and Treatment: Perspectives and Prospects". J Nerv Ment Dis. 183 (3): 127–138. doi:10.1097/00005053-199503000-00002. PMID   7891058. Cyproheptadine, a 5-HT2A c antagonist (Hoyer and Schoeffter, 1991), prevented the subjective effects of DMT in two of three normal volunteers (Meltzer et al., 1982).
  33. ↑ Meltzer HY, Wiita B, Tricou BJ, Simonovic M, Fang VS, Manov G (1982). "Effect of Serotonin Precursors and Serotonin Agonists on Plasma Hormone Levels". In Beng T. Ho (ed.). Serotonin in Biological Psychiatry. Books on Demand. pp. 128–133. ISBN   978-0-608-00638-3.
  34. 1 2 Strassman R (1 December 2000). DMT: The Spirit Molecule: A Doctor's Revolutionary Research into the Biology of Near-Death and Mystical Experiences. Simon and Schuster. ISBN   978-1-59477-973-2 . Retrieved 9 July 2025. The next serotonin receptor blockade study used cyproheptadine, an antihistamine drug with additional anti-serotonin properties. In this case, cyproheptadine prevents drugs from attaching to the serotonin "2" site, the receptor researchers believe is the most important in controlling how psychedelics work. This protocol was identical in design to that of the pindolol study in that volunteers received cyproheptadine several hours before DMT. Eight volunteers completed this study. Most were new recruits. There appeared to be some suppression of effects, so we gave the high dose, 0.4 mg/kg, with and without the serotonin blocker. Because cyproheptadine clearly did not magnify DMT's effects, we hoped that using this large dose would give us the best chance of establishing a significant level of DMT suppression. However, the sedating properties of the drug were so pronounced that they complicated interpretation of the data. It was difficult to tell how much was specific DMT blockade, and how much was general tranquilization.
  35. ↑ Halberstadt AL, Geyer MA (September 2011). "Multiple receptors contribute to the behavioral effects of indoleamine hallucinogens". Neuropharmacology. 61 (3): 364–381. doi:10.1016/j.neuropharm.2011.01.017. PMC   3110631 . PMID   21256140. The mechanism for the subjective effects of DMT has also been investigated clinically. Blockade studies with low doses of the nonselective 5-HT2 antagonist cyproheptadine produced inconclusive results (Tueting et al., 1992), and the sedative effects of cyproheptadine precluded testing higher doses (Strassman, 2001).
  36. 1 2 Winter JC (1994). "The stimulus effects of serotonergic hallucinogens in animals". NIDA Res Monogr. 146: 157–182. PMID   8742798. Figures 5 through 7 show the agonistic effects (upper panels) and the antagonistic effects (lower panels) of a series of serotonergic antagonists in rats trained with LSD as a discriminative stimulus. It is obvious that a full spectrum of activity is represented. Methysergide, cyproheptadine, and mianserin are significantly LSD-like (figure 5, upper panel) and are, as would be expected from their agonistic effects, only marginally effective as antagonists (lower panel). [...] Agonist and antagonist effects of methysergide, cyproheptadine, and minaserin in rats trained with LSD [0.16 mg/kg] and saline. [...] Of the three purported antagonists showing the highest degree of LSD-like stimulus effects in the rat, two—methysergide and cyproheptadine—are claimed to be sometimes associated with hallucinations in humans.
  37. ↑ 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.
  38. ↑ Liu T. "BindingDB BDBM50017721 1-Methyl-4-(5H-dibenzo(a,d)cycloheptenylidene)piperidine::1-methyl-4-(5-dibenzo(a,e)cycloheptatrienylidene)piperidine::4-(5-dibenzo(a,d)cyclohepten-5-ylidine)-1-methylpiperidine::4-(5H-dibenzo(a,d)cyclohepten-5-ylidene)-1-methylpiperidine::4-(5H-dibenzo[a,d][7]annulen-5-ylidene)-1-methylpiperidine4-(5H-dibenzo[a,d]cyclohepten-5-ylidene)-1-methylpiperidine::5-(1-methylpiperidylidene-4)-5H-dibenzo(a,d)cyclopheptene::CHEMBL516::CYPROHEPTADINE". BindingDB. Retrieved 6 December 2024.
  39. ↑ Young R, Khorana N, Bondareva T, Glennon RA (October 2005). "Pizotyline effectively attenuates the stimulus effects of N-methyl-3,4-methylenedioxyamphetamine (MDMA)". Pharmacol Biochem Behav. 82 (2): 404–410. doi:10.1016/j.pbb.2005.09.010. PMID   16253319.
  40. 1 2 Gillman PK (1999). "The serotonin syndrome and its treatment". Journal of Psychopharmacology. 13 (1): 100–109. doi:10.1177/026988119901300111. PMID   10221364. S2CID   17640246.
  41. ↑ Sporer KA (August 1995). "The serotonin syndrome. Implicated drugs, pathophysiology and management". Drug Safety. 13 (2): 94–104. doi:10.2165/00002018-199513020-00004. PMID   7576268. S2CID   19809259.
  42. ↑ Kapur S, Zipursky RB, Jones C, Wilson AA, DaSilva JD, Houle S (June 1997). "Cyproheptadine: a potent in vivo serotonin antagonist". The American Journal of Psychiatry. 154 (6): 884a–884. doi:10.1176/ajp.154.6.884a. PMID   9167527.
  43. ↑ Segelcke D, Messlinger K (April 2017). "Putative role of 5-HT2B receptors in migraine pathophysiology". Cephalalgia. 37 (4): 365–371. doi:10.1177/0333102416646760. PMID   27127104.
  44. 1 2 Heym J, Jacobs BL (1987). "Serotonergic mechanisms of hallucinogenic drug effects". Monogr Neural Sci. Frontiers of Neurology and Neuroscience. 13: 55–81. doi:10.1159/000414570. ISBN   978-3-8055-4561-7. PMID   2891030. Several studies have found classical serotonin antagonists such as cinanserin, cyproheptadine and methysergide to be effective blockers of the discriminative stimulus properties of hallucinogens, including DOM, mescaline, and LSD [20, 22, 23, 38, 58, 98, 109]. [...] In addition, many of the classical antagonists display a complex effect in the drug discrimination paradigm [23]. Low doses of methysergide, mianserin and cyproheptadine, for example, have been reported to only partially antagonize an LSD cue while higher doses of these same compounds actually show a partial generalization to the LSD stimulus [23]. This latter finding suggests that at high doses these antagonists are perceived to some extent as LSD. Perhaps this explains the clinical experience with methysergide where psychoactive effects have been noted [82].
  45. ↑ Appel JB, West WB, Buggy J (January 2004). "LSD, 5-HT (serotonin), and the evolution of a behavioral assay". Neurosci Biobehav Rev. 27 (8): 693–701. doi:10.1016/j.neubiorev.2003.11.012. PMID   15019419. The structural congeners of LSD, BOL and methysergide (UML) blocked the LSD cue partially (30% of control) as did another centrally acting 5-HT antagonist, cyproheptadine; the peripherally acting 5-HT antagonist xylamidine had no effect at any dose tested.
  46. ↑ Marona-Lewicka D, Nichols DE (October 2007). "Further evidence that the delayed temporal dopaminergic effects of LSD are mediated by a mechanism different than the first temporal phase of action". Pharmacol Biochem Behav. 87 (4): 453–461. doi:10.1016/j.pbb.2007.06.001. PMID   17618679. Combination tests (Tables 5 and 6) with the highly selective 5-HT2A antagonist, MDL 11,393 confirmed that a 5-HT2A antagonist effectively blocks only the LSD-30, and not the LSD-90 cue. Even the nonselective 5-HT antagonist, cyproheptadine, which significantly inhibited the LSD-30 effect (Table 6), had no effect against the LSD-90 cue (Table 5). Thus, we provide further evidence that activation of the 5-HT2A receptor is not essential for the delayed effect of LSD treatment
  47. ↑ Glennon RA (1988). "Site-Selective Serotonin Agonists as Discriminative Stimuli". Transduction Mechanisms of Drug Stimuli. Vol. 4. pp. 15–31. doi:10.1007/978-3-642-73223-2_2. ISBN   978-3-642-73225-6. PMID   3293039.{{cite book}}: |journal= ignored (help)
  48. ↑ Halberstadt AL, Geyer MA (2018). "Effect of Hallucinogens on Unconditioned Behavior". Behavioral Neurobiology of Psychedelic Drugs. Curr Top Behav Neurosci. Vol. 36. pp. 159–199. doi:10.1007/7854_2016_466. ISBN   978-3-662-55878-2. PMC   5787039 . PMID   28224459. The 5-HT2A receptor is believed to be responsible for the hallucinogen HTR. It was reported as early as 1967 that the nonselective 5-HT antagonists methysergide and cyproheptadine block the ability of LSD and other hallucinogens to induce the HTR (Corne and Pickering 1967); subsequent studies confirmed that many other 5-HT antagonists ameliorate the response.
  49. ↑ Glennon RA (1992). "Animal Models for Assessing Hallucinogenic Agents". Animal Models of Drug Addiction. Vol. 24. Totowa, NJ: Humana Press. pp. 345–381. doi:10.1385/0-89603-217-5:345. ISBN   978-1-59259-629-4. 5-HTP-induced head-twitch in rodents can be antagonized by a wide variety of 5-HT antagonists, including cinanserin, cyproheptadine, metergoline, methysergide, and mianserin (Come et al., 1963; Bedard and Pycock, 1977; Ortmann et al., 1982; Colpaert and Janssen, 1983; Green, 1984; Lucki et al., 1984; Gerber et al., 1985). In the rat, cyproheptadine also antagonizes the head-twitch induced by LSD (Vetulani et al., 1980; Lucki et al., 1984), quipazine (Vetulani et al., 1980), and 5-OMe-DMT (Matthews and Smith, 1980). [...] Examining eight 5-HT antagonists (2-bromo LSD, cinanserin, cyproheptadine, methiothepin, methysergide, metergoline, mianserin, pizotifen), Colpaert and Janssen (1983) found that all blocked 5-HTP-induced head-twitch in the rat, but did so in a biphasic manner. There is an initial sharp decrease in response frequency followed by a further, but shallower, rate of decrease. [...]
  50. 1 2 Winter JC (April 2009). "Hallucinogens as discriminative stimuli in animals: LSD, phenethylamines, and tryptamines". Psychopharmacology (Berl). 203 (2): 251–263. doi:10.1007/s00213-008-1356-8. PMID   18979087. Two factors complicated this simple picture; the second of these was yet to appear but the first was evident at the time. The antagonists then available, drugs such as cinanserin, methysergide, cyproheptadine, mianserin, and pizotyline (BC-105), were nonselective with respect to other neurotransmitter systems and, indeed, some had behaviorally evident partial agonist effects in LSD-trained rats (Colpaert et al. 1982).
  51. ↑ Stephenson JD (1 January 1990). "Neuropharmacological Studies of the Serotonergic System". International Review of Psychiatry. 2 (2): 157–178. doi:10.3109/09540269009028280. ISSN   0954-0261. Several 5-HT antagonists had partial LSD-like agonist activity and were therefore only weakly effective as antagonists of the LSD cue (Colpaert et al., 1982). These compounds included metergoline, methysergide, cyproheptadine, metetepine and cinanserin.
  52. ↑ Colpaert FC, Niemegeers CJ, Janssen PA (April 1982). "A drug discrimination analysis of lysergic acid diethylamide (LSD): in vivo agonist and antagonist effects of purported 5-hydroxytryptamine antagonists and of pirenperone, a LSD-antagonist". J Pharmacol Exp Ther. 221 (1): 206–214. doi:10.1016/S0022-3565(25)33038-7. PMID   7062283.
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  56. 1 2 Dabaghzadeh F, Khalili H, Ghaeli P, Dashti-Khavidaki S (December 2012). "Potential benefits of cyproheptadine in HIV-positive patients under treatment with antiretroviral drugs including efavirenz". Expert Opinion on Pharmacotherapy. 13 (18): 2613–2624. doi:10.1517/14656566.2012.742887. PMID   23140169. S2CID   25769557.
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  60. 1 2 Dowling PM (8 February 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   978-0-911910-50-6. Archived from the original on 4 March 2016. Retrieved 26 October 2008.
  61. ↑ Dowling PM (8 February 2005). "Drugs Affecting Appetite". In Kahn CM, Line S, Aiello SE (eds.). The Merck Veterinary Manual (9th ed.). John Wiley & Sons. ISBN   978-0-911910-50-6. Archived from the original on 28 October 2012. Retrieved 26 October 2008.
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