塞浦西他啶

化合物

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,也是兒童抗過敏藥水希普利敏的主要成分。

塞浦西他啶
臨床資料
读音(/ˌsprˈhɛptədn/[1]
商品名英语Drug nomenclaturePeriactin, others
AHFS/Drugs.comMonograph
MedlinePlusa682541
核准狀況
懷孕分級
  • : A
给药途径Oral
ATC碼
法律規範狀態
法律規範
藥物動力學數據
血漿蛋白結合率96 to 99%
药物代谢Hepatic,[3][4] mostly CYP3A4 mediated.
生物半衰期8.6 hours[2]
排泄途徑糞便 (2–20%; of which, 34% as unchanged drug) 與 (40%; none as unchanged drug)[3][4]
识别信息
  • 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-methylpiperidine
CAS号129-03-3  checkY
969-33-5盐酸盐
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard英语CompTox Chemicals Dashboard (EPA)
ECHA InfoCard100.004.482 編輯維基數據鏈接
化学信息
化学式C21H21N
摩尔质量287.41 g·mol−1
3D模型(JSmol英语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 checkY
  • Key:JJCFRYNCJDLXIK-UHFFFAOYSA-N checkY

它於1959年獲得專利,並於1961年用於醫療使用。[5]

醫療使用

 
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

副作用包括:[3][4]

  • 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
  • 兴奋 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)
  • 心悸 Palpitation
  • 期前收缩 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
  • 抗胆碱能副作用:
    • 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
    • 排尿困难 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

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 。[3][4]

藥理

藥效學

塞浦西他啶对此表列出的所有受体均表现为拮抗剂逆向激动剂[20]

塞浦西他啶[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

塞浦西他啶是一种非常有效的抗组胺药H1受体拮抗剂。它在较高浓度下还具有抗胆碱能抗血清素能抗多巴胺能活性。它是5-HT2受体的强效拮抗剂,这是其治疗血清素综合症的基础。

塞浦西他啶具有较弱的的抗雄激素活性。[21]

藥物代謝動力學

塞浦西他啶口服後吸收良好,血漿濃度峰值出現在1至3小時後。[22]口服塞浦西他啶的生物半衰期約為8小時。[2]

化學

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

研究

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]

塞浦西他啶已被研究用於創傷後壓力症候群(PTSD)。[24]

獸醫用途

塞浦西他啶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]它在貓的生物半衰期為 12 小時。[27]

塞浦西他啶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

  1. ^ Cyproheptadine. Dictionary.com Unabridged. Random House. 
  2. ^ 2.0 2.1 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. 
  3. ^ 3.0 3.1 3.2 3.3 CYPROHEPTADINE HYDROCHLORIDE tablet [Boscogen, Inc.]. DailyMed. Boscogen, Inc. November 2010 [26 October 2013]. (原始内容 (PDF)存档于2013-07-04). 
  4. ^ 4.0 4.1 4.2 4.3 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). 
  5. ^ Fischer, Jnos; Ganellin, C. Robin. Analogue-based Drug Discovery. John Wiley & Sons. 2006: 547 [2020-12-15]. ISBN 9783527607495. (原始内容存档于2021-08-29) (英语). 
  6. ^ MedlinePlus Drug Information: Cyproheptadine. [2020-12-15]. (原始内容存档于2008-10-01). 
  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 . PMID 27423188. doi:10.1186/s13052-016-0272-5. 
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  13. ^ Pfendner, Ellen G.; Bruckner, Anna L. Epidermolysis Bullosa Simplex. GeneReviews. October 13, 2016 [2020-12-15]. PMID 20301543. (原始内容存档于2020-10-22). 
  14. ^ Ciproheptadina, estimulante del apetito (Cyproheptadine, appetite stimulant). [2020-12-15]. (原始内容存档于2020-10-24). 
  15. ^ Bioplex NF. [2020-12-15]. (原始内容存档于2018-04-18). 
  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. 
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  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 . 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]. (原始内容存档于2021-08-28). 
  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. (原始内容存档于2014-01-01). 
  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 [2022-06-16]. ISBN 978-0-911910-50-6. (原始内容存档于2016-03-04).  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 [2022-06-16]. ISBN 978-0-911910-50-6. (原始内容存档于2012-10-28).  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]. (原始内容存档于2016-03-03). 

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