塞浦西他啶

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塞浦西他啶
Cyproheptadine.svg
Cyproheptadine-Spartan-PM3-3D-balls.png
系统(IUPAC)命名名称
4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-methylpiperidine
临床数据
读音(/ˌsprˈhɛptədn/[1]
商品名Periactin, others
Drugs.comMonograph
MedlinePlusa682541
医疗法规
妊娠分级
  • AU: A
  • US: B (非人类研究中表明无风险)
给药途径Oral
合法狀態
合法状态
药代动力学数据
蛋白结合度96至99%
代谢Hepatic,[2][3] mostly CYP3A4 mediated.
生物半衰期8.6 hours[4]
排泄糞便 (2–20%; of which, 34% as unchanged drug) 與 (40%; none as unchanged drug)[2][3]
识别信息
CAS注册号129-03-3969-33-5 (hydrochloride))  ✓
ATC代码R06AX02
PubChemCID 2913
IUPHAR/BPS英语IUPHAR/BPS277
DrugBankDB00434 ✓
ChemSpider2810 ✓
UNII2YHB6175DO ✓
KEGGD07765 ✓
ChEBICHEBI:4046 ✓
ChEMBL英语ChEMBLCHEMBL516 ✓
化学信息
化学式C21H21N
摩尔质量287.41 g·mol−1

塞浦西他啶(Cyproheptadine),或名賽庚啶 ,是第一代抗組織胺藥,具有抗乙醯膽鹼局部麻醉的功能。

它於1959年獲得專利,並於1961年用於醫療使用。[5]

醫療使用[编辑]

Periactin (cyproheptadine) 4 mg tablets
塞浦西他啶(Cyproheptadine)的3D分子結構表示為 空間填充模型

副作用[编辑]

副作用包括:[2][3]

  • 鎮靜和困倦(通常是短暫的)Sedation and sleepiness (often transient)
  • 頭暈 Dizziness
  • 協調不佳 Disturbed coordination
  • 混亂 Confusion
  • 躁動不安 Restlessness
  • Excitation
  • 緊張 Nervousness
  • 震顫 Tremor
  • 易怒 Irritability
  • 失眠 Insomnia
  • 感覺異常 Paresthesias
  • 神經炎 Neuritis
  • 抽搐 Convulsions
  • 欣快感 Euphoria
  • 幻覺 Hallucinations
  • 歇斯底里 Hysteria
  • 模糊 Faintness
  • 皮疹和水腫的過敏表現 Allergic manifestation of rash and edema
  • 發汗 Diaphoresis
  • 蕁麻疹 Urticaria
  • 對光敏感 Photosensitivity
  • 急性迷路炎 Acute labyrinthitis
  • 複視(雙眼) Diplopia (seeing double)
  • 眩暈 Vertigo
  • 耳鳴 Tinnitus
  • 低血壓 Hypotension (low blood pressure)
  • Palpitation
  • Extrasystoles
  • 過敏性休克 Anaphylactic shock
  • 溶血性貧血 Hemolytic anemia
  • 諸如白细胞减少症粒細胞缺乏症血小板減少症等血液異常 Blood dyscrasias such as leukopenia, agranulocytosis and thrombocytopenia
  • 膽汁淤積 Cholestasis
  • 對肝臟的影響:
  • 上腹窘迫 Epigastric distress
  • 食欲不振 Anorexia
  • 噁心 Nausea
  • 嘔吐 Vomiting
  • 腹瀉 Diarrhea
  • Anticholinergic side effects such as:
    • 視力模糊 Blurred vision
    • 便秘 Constipation
    • 口腔乾燥症(口乾) Xerostomia (dry mouth)
    • 心動過速(高心率)Tachycardia (high heart rate)
    • 尿瀦留 Urinary retention
    • Difficulty passing urine
    • 鼻塞 Nasal congestion
    • 鼻或喉嚨乾燥 Nasal or throat dryness
  • 頻尿 Urinary frequency
  • 早期月經 Early menses
  • 支氣管分泌物增厚 Thickening of bronchial secretions
  • 胸悶氣喘 Tightness of chest and wheezing
  • 疲勞 Fatigue
  • 寒意 Chills
  • 頭痛 Headache
  • 食慾增加 Increased appetite
  • 體重增加 Weight gain

用藥過量[编辑]

過量使用時,有時建議使用活性炭進行洗胃。這些症狀通常表明中樞神經系統抑制(或在某些情況下相反地刺激中樞神經系統)和過度的抗膽鹼能副作用。小鼠的半數致死量(LD50)為 123 mg/kg,,大鼠的半數致死量為 295 mg/kg 。[2][3]

藥理[编辑]

藥效學[编辑]

Cyproheptadine[20]
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
SERT 4,100 Rat
NET 290 Rat
DAT ND ND
  1. ^ 平衡常数越小,藥物與位點的結合越强。
  2. ^
    • ↑促效劑
    • ↓抗拮劑

Cyproheptadine is a very potent antihistamine or antagonist 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, and this underlies its effectiveness in the treatment of serotonin syndrome.

Cyproheptadine is known to be an antagonist or inverse agonist of all of the receptors listed in the adjacent table.[20]

塞浦西他啶(Cyproheptadine)的抗雄激素活性較弱。[21]

藥物代謝動力學[编辑]

塞浦西他啶(Cyproheptadine)口服後吸收良好,血漿濃度峰值出現在1至3小時後。[22]口服塞浦西他啶(Cyproheptadine)的最終半衰期約為8小時。[4]

化學[编辑]

塞浦西他啶(Cyproheptadine)是三環英语Tricyclic苯並環庚烯英语Benzocycloheptene,與吡唑替芬英语Pizotifen酮替芬英语Ketotifen以及三環抗抑鬱藥密切相關。

研究[编辑]

在一項規模較小的精神分裂症患者中,輔助使用塞浦西他啶(Cyproheptadine)作為輔助治療,該患者的病情穩定且正在接受其他藥物治療。雖然注意力和口語流利性似乎有所改善,但這項研究規模太小,不足以概括。[23]在另兩項針對精神分裂症患者的試驗中,也已對其進行了佐劑研究,總共約有50人,並且似乎沒有效果。[24]

已經進行了一些試驗,以觀察塞浦西他啶(Cyproheptadine)是否可以減輕SSRI和抗精神病藥引起的性功能障礙。[25]

塞浦西他啶(Cyproheptadine)已被研究用於創傷後壓力症候群(PTSD)。[24]

獸醫用途[编辑]

塞浦西他啶(Cyproheptadine)使用在貓的食慾刺激劑英语appetite stimulant[26] ,也可作為哮喘的輔助治療劑。[27] 可能的副作用包括刺激和攻擊行為。[28] 塞浦西他啶(Cyproheptadine)在貓的生物半衰期為 12 小時。[27]

塞浦西他啶(Cyproheptadine)也用在馬的垂體中間部功能障礙英语pituitary pars intermedia dysfunction的二線治療。[29][30]

參考資料[编辑]

  1. ^ Cyproheptadine. Dictionary.com Unabridged. Random House. 
  2. ^ 2.0 2.1 2.2 2.3 CYPROHEPTADINE HYDROCHLORIDE tablet [Boscogen, Inc.] (PDF). DailyMed. Boscogen, Inc. November 2010 [26 October 2013]. 
  3. ^ 3.0 3.1 3.2 3.3 PRODUCT INFORMATION PERIACTIN® (cyproheptadine hydrochloride) (PDF). Aspen Pharmacare Australia. Aspen Pharmacare Australia Pty Ltd. 17 November 2011 [26 October 2013]. (原始内容 (PDF)存档于29 October 2013). 
  4. ^ 4.0 4.1 Gunja N, Collins M, Graudins A. A comparison of the pharmacokinetics of oral and sublingual cyproheptadine. Journal of Toxicology. Clinical Toxicology. 2004, 42 (1): 79–83. PMID 15083941. S2CID 20196551. doi:10.1081/clt-120028749. 
  5. ^ Fischer, Jnos; Ganellin, C. Robin. Analogue-based Drug Discovery. John Wiley & Sons. 2006: 547. ISBN 9783527607495 (英语). 
  6. ^ MedlinePlus Drug Information: Cyproheptadine
  7. ^ 7.0 7.1 De Bruyne, P; Christiaens, T; Boussery, K; Mehuys, E; Van Winckel, M. Are antihistamines effective in children? A review of the evidence. Archives of Disease in Childhood. January 2017, 102 (1): 56–60. PMID 27335428. S2CID 21185048. doi:10.1136/archdischild-2015-310416. 
  8. ^ Saito, Y; Yamanaka, G; Shimomura, H; Shiraishi, K; Nakazawa, T; Kato, F; Shimizu-Motohashi, Y; Sasaki, M; Maegaki, Y. Reconsideration of the diagnosis and treatment of childhood migraine: A practical review of clinical experiences. Brain & Development. May 2017, 39 (5): 386–394. PMID 27993427. S2CID 34703034. doi:10.1016/j.braindev.2016.11.011. 
  9. ^ Salvatore, S; Barberi, S; Borrelli, O; Castellazzi, A; Di Mauro, D; Di Mauro, G; Doria, M; Francavilla, R; Landi, M; Martelli, A; Miniello, VL; Simeone, G; Verduci, E; Verga, C; Zanetti, MA; Staiano, A; SIPPS Working Group on, FGIDs. Pharmacological interventions on early functional gastrointestinal disorders. Italian Journal of Pediatrics. 16 July 2016, 42 (1): 68. PMC 4947301可免费查阅. PMID 27423188. doi:10.1186/s13052-016-0272-5. 
  10. ^ Taylor, David; Paton, Carol; Kapur, Shitij. The Maudsley Prescribing Guidelines in Psychiatry. John Wiley & Sons. 2015: 85. ISBN 9781118754573 (英语). 
  11. ^ Szepietowski, JC; Reszke, R. Psychogenic Itch Management. Current Problems in Dermatology 50. 2016: 124–32. ISBN 978-3-318-05888-8. PMID 27578081. doi:10.1159/000446055. 
  12. ^ Ashton AK, Weinstein WL. Cyproheptadine for drug-induced sweating. American Journal of Psychiatry. May 2002, 159 (5): 874–5. PMID 11986151. doi:10.1176/appi.ajp.159.5.874-a. 
  13. ^ Pfendner, Ellen G.; Bruckner, Anna L. Epidermolysis Bullosa Simplex. GeneReviews. October 13, 2016. PMID 20301543. 
  14. ^ Ciproheptadina, estimulante del apetito (Cyproheptadine, appetite stimulant)
  15. ^ Bioplex NF
  16. ^ Harrison ME, Norris ML, Robinson A, Spettigue W, Morrissey M, Isserlin L. Use of cyproheptadine to stimulate appetite and body weight gain: A systematic review.. Appetite. 2019, 137: 62–72. PMID 30825493. S2CID 72333631. doi:10.1016/j.appet.2019.02.012. 
  17. ^ Rossi, S (编). Australian Medicines Handbook 2013. Adelaide: The Australian Medicines Handbook Unit Trust. 2013. ISBN 978-0-9805790-9-3. 
  18. ^ Iqbal, MM; Basil, MJ; Kaplan, J; Iqbal, MT. Overview of serotonin syndrome. Annals of Clinical Psychiatry. November 2012, 24 (4): 310–8. PMID 23145389. 
  19. ^ Chertoff, Jason. Cyproheptadine-Induced Acute Liver Failure. ACG Case Reports Journal. 8 July 2014, 1 (4): 212–213. PMC 4286888可免费查阅. PMID 25580444. doi:10.14309/crj.2014.56. 
  20. ^ 20.0 20.1 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. [14 August 2017]. 
  21. ^ Pucci E, Petraglia F. Treatment of androgen excess in females: yesterday, today and tomorrow. Gynecol. Endocrinol. December 1997, 11 (6): 411–33. PMID 9476091. doi:10.3109/09513599709152569. 
  22. ^ Lindsay Murray; Frank Daly; David McCoubrie; Mike Cadogan. Toxicology Handbook. Elsevier Australia. 15 January 2011: 388 [27 November 2011]. ISBN 978-0-7295-3939-5. 
  23. ^ Buoli, M; Altamura, AC. May non-antipsychotic drugs improve cognition of schizophrenia patients?. Pharmacopsychiatry. March 2015, 48 (2): 41–50. PMID 25584772. doi:10.1055/s-0034-1396801. 
  24. ^ 24.0 24.1 Dabaghzadeh, F; Khalili, H; Ghaeli, P; Dashti-Khavidaki, S. Potential benefits of cyproheptadine in HIV-positive patients under treatment with antiretroviral drugs including efavirenz. Expert Opinion on Pharmacotherapy. December 2012, 13 (18): 2613–24. PMID 23140169. S2CID 25769557. doi:10.1517/14656566.2012.742887. 
  25. ^ Nunes, LV; Moreira, HC; Razzouk, D; Nunes, SO; Mari Jde, J. Strategies for the treatment of antipsychotic-induced sexual dysfunction and/or hyperprolactinemia among patients of the schizophrenia spectrum: a review. Journal of Sex & Marital Therapy. 2012, 38 (3): 281–301. PMID 22533871. S2CID 23406005. doi:10.1080/0092623X.2011.606883. 
  26. ^ Agnew, W; Korman, R. Pharmacological appetite stimulation: rational choices in the inappetent cat. Journal of Feline Medicine and Surgery. September 2014, 16 (9): 749–56. PMID 25146662. S2CID 37126352. doi:10.1177/1098612X14545273. 
  27. ^ 27.0 27.1 Dowling PM. Systemic Therapy of Airway Disease: Cyproheptadine. Kahn CM, Line S, Aiello SE (编). The Merck Veterinary Manual 9th. John Wiley & Sons. February 8, 2005. ISBN 978-0-911910-50-6.  Retrieved on October 26, 2008.
  28. ^ Dowling PM. Drugs Affecting Appetite. Kahn CM, Line S, Aiello SE (编). The Merck Veterinary Manual 9th. John Wiley & Sons. February 8, 2005. ISBN 978-0-911910-50-6.  Retrieved on October 26, 2008.
  29. ^ Durham, AE. Therapeutics for Equine Endocrine Disorders. The Veterinary Clinics of North America. Equine Practice. April 2017, 33 (1): 127–139. PMID 28190613. doi:10.1016/j.cveq.2016.11.003. 
  30. ^ Merck Vet Manual. Hirsutism Associated with Adenomas of the Pars Intermedia. [April 24, 2011].