磷酸二酯酶4抑制劑
PDE4抑制劑,磷酸二酯酶4抑制劑,是一種用於阻斷磷酸二酯酶4 (PDE4)對環磷酸腺苷(cAMP)降解作用的藥物。PDE4 酶是免疫細胞中最常見的 PDE。它們主要負責水解免疫細胞和中樞神經系統細胞內的 cAMP。 [1]
治療作用
PDE4D 抑制和PDE4A抑制似乎也與 PDE4 抑制劑的抗抑鬱作用有關。 [2]同樣, PDE4B抑制似乎是 PDE4 抑制劑的抗精神病作用所必需的, [3]與這一觀點一致,在一項研究中,PDE4B 多態性和中樞神經系統基因表達的改變與精神分裂症和雙相情感障礙有關。 [4] PDE4 還調節額葉皮質中的D1/PKA/DARPP-32信號級聯,這可能有助於 PDE4 抑制劑的抗精神病和促認知作用。 [5]而PDE4C主要在外周表達,因此可能是 PDE4 抑制劑的外周作用(例如其抗炎作用)的部分原因。 [2]眾所周知,PDE4 抑制可減弱大鼠對乙醇的尋求和消耗, [6]因此表明其在治療酒精依賴方面可能具有實用性。事實上,一項實驗發現,與服用安慰劑的人相比,嚴重飲酒者服用治療牛皮癬的 PDE4 口服藥物可顯着減少飲酒量。 [7]一些不同的證據表明其在治療腦腫瘤中的治療效用。 [8]
已知 PDE4 抑制劑具有促認知(包括改善長期記憶)、 [9]促進覺醒、 [10]神經保護、 [11] [12]和抗炎作用。 [13]因此,PDE4 抑制劑已被研究作為多種不同疾病的治療方法,包括中樞神經系統疾病,如重度抑鬱症(臨床抑鬱症)、焦慮症、精神分裂症、 [14] [15]帕金森病、 [16]阿爾茨海默病疾病, [17]多發性硬化症, [18]注意力缺陷多動障礙,亨廷頓舞蹈病,中風,自閉症和炎症性疾病,例如慢性阻塞性肺病(COPD),哮喘和類風濕性關節炎。 [19] [3] [2]典型的 PDE4 抑制劑是咯利普蘭。
不良反應
PDE4抑制劑的臨床開發因其強大的催吐作用而受到阻礙,這似乎與它們對後區表達的PDE4D的抑制有關。 [2]
噁心、嘔吐和相關的一般胃腸道副作用是 PDE4 抑制劑最常見的副作用。其他可能的副作用包括呼吸道和泌尿道感染,這些副作用是在羅氟司特的臨床使用中發現的。 [20]
例子
- 木犀草素,從花生和其他植物中提取的補充劑,也具有IGF-1特性。 [21]
- Mesembrenone是一種來自草本植物Sceletium tortuosum (Kanna) 的生物鹼。
- Piclamilast是Apremilast是一種鄰苯二甲酰亞胺衍生物,於 2014 年 3 月被美國 FDA 批准用於治療銀屑病關節炎[22] ,並於 2014 年 9 月被批准用於治療斑塊型銀屑病,商品名為Otezla 。 [23]
- 西洛司特,用於治療慢性阻塞性肺病。 [24]
- Crisaborole (AN2728),一種含硼藥物,用於局部治療牛皮癬和特應性皮炎。 [25] [26]它於2016年12月14日獲得FDA批准,商品名為Eucrisa ,用於治療2歲及以上患者的輕至中度特應性皮炎(濕疹)。 [27]
- 咖啡因是一種弱的、非選擇性的 PDE 抑制劑。 [28]咖啡因的代謝產物茶鹼是一種更有效的 PDE 抑制劑。 [28]
- 地西泮,一種苯二氮卓類抗焦慮劑、遺忘劑、催眠劑、鎮靜劑和肌肉鬆弛劑。 [29]
- Glaucine是一種阿朴啡生物鹼、低效 PDE4 抑制劑、鈣通道阻滯劑、多巴胺拮抗劑和5-HT2A正變構調節劑,在東歐和冰島用作鎮咳藥。
- Ibudilast是一種神經保護劑和支氣管擴張劑藥物,主要用於治療哮喘和中風。它最大程度地抑制 PDE4,但也顯示出對其他 PDE 亞型的顯着抑制作用,因此根據劑量可充當選擇性 PDE4 抑制劑或非選擇性磷酸二酯酶抑制劑。
- 一種比咯利普蘭更有效的抑制劑。 [30]
- Roflumilast ,獲得許可用於治療嚴重慢性阻塞性肺病,以及用於治療斑塊狀銀屑病。 [31]
- 咯利普蘭,用作藥理學研究的調查工具。
- Mesembrine是一種存在於Sceletium tortuosum (kanna) 中的生物鹼。
作用機理
抑制PDE4可阻止cAMP水解,從而增加細胞內cAMP的水平。[來源請求]
參考文獻
- ^ Spina, D. PDE4 inhibitors: current status. British Journal of Pharmacology. 2008, 155 (3): 308–315. PMC 2567892 . PMID 18660825. doi:10.1038/bjp.2008.307.
- ^ 2.0 2.1 2.2 2.3 Houslay, MD; Conti, M (編). Phosphodiesterases as Drug Targets (PDF). Handbook of Experimental Pharmacology 204. Springer Berlin Heidelberg. 2011. ISBN 978-3-642-17968-6. doi:10.1007/978-3-642-17969-3.
|editor-last=
和|editor1=
只需其一 (幫助); Editors list列表缺少|last2=
(幫助) [失效連結] - ^ 3.0 3.1 Halene, TB; Siegel, SJ. PDE inhibitors in psychiatry – future options for dementia, depression and schizophrenia?. Drug Discovery Today. October 2007, 12 (19–20): 870–878. PMID 17933689. doi:10.1016/j.drudis.2007.07.023.
- ^ Fatemi, SH; King, DP; Reutiman, TJ; Folsom, TD; Laurence, JA; Lee, S; Fan, YT; Paciga, SA; Conti, M; Menniti, FS. PDE4B polymorphisms and decreased PDE4B expression are associated with schizophrenia. Schizophrenia Research. April 2008, 101 (1–3): 36–49. PMID 18394866. S2CID 32661995. doi:10.1016/j.schres.2008.01.029.
- ^ Kuroiwa, M; Snyder, GL; Shuto, T; Fukuda, A; Yanagawa, Y; Benavides, DR; Nairn, AC; Bibb, JA; Greengard, P; Nishi, A. Phosphodiesterase 4 inhibition enhances the dopamine D1 receptor/PKA/DARPP-32 signaling cascade in frontal cortex. Psychopharmacology. February 2012, 219 (4): 1065–1079. PMC 3539205 . PMID 21833500. doi:10.1007/s00213-011-2436-8.
- ^ Wen, RT; Zhang, M; Qin, WJ; Liu, Q; Wang, WP; Lawrence, AJ; Zhang, HT; Liang, JH. The Phosphodiesterase-4 (PDE4) Inhibitor Rolipram Decreases Ethanol Seeking and Consumption in Alcohol-Preferring Fawn-Hooded Rats. Alcoholism: Clinical and Experimental Research. December 2012, 36 (12): 2157–2167. PMC 4335658 . PMID 22671516. doi:10.1111/j.1530-0277.2012.01845.x.
- ^ Wilson, C. (2021). Psoriasis drug may cut alcohol misuse. New Scientist, 250(3340), p.16
- ^ Sengupta, R; Sun, T; Warrington, NM; Rubin, JB. Treating brain tumors with PDE4 inhibitors. Trends in Pharmacological Sciences. June 2011, 32 (6): 337–344. PMC 3106141 . PMID 21450351. doi:10.1016/j.tips.2011.02.015.
- ^ Barad M, Bourtchouladze R, Winder DG, Golan H, Kandel E. Rolipram, a type IV-specific phosphodiesterase inhibitor, facilitates the establishment of long-lasting long-term potentiation and improves memory. Proceedings of the National Academy of Sciences of the United States of America. 1998, 95 (25): 15020–5. Bibcode:1998PNAS...9515020B. PMC 24568 . PMID 9844008. doi:10.1073/pnas.95.25.15020 .
- ^ Lelkes Z, Alföldi P, Erdos A, Benedek G. Rolipram, an antidepressant that increases the availability of cAMP, transiently enhances wakefulness in rats. Pharmacology Biochemistry and Behavior. 1998, 60 (4): 835–9. PMID 9700966. S2CID 37020086. doi:10.1016/S0091-3057(98)00038-0.
- ^ Block F, Schmidt W, Nolden-Koch M, Schwarz M. Rolipram reduces excitotoxic neuronal damage. NeuroReport. 2001, 12 (7): 1507–11. PMID 11388438. S2CID 2768440. doi:10.1097/00001756-200105250-00041.
- ^ Chen RW, Williams AJ, Liao Z, Yao C, Tortella FC, Dave JR. Broad spectrum neuroprotection profile of phosphodiesterase inhibitors as related to modulation of cell-cycle elements and caspase-3 activation. Neuroscience Letters. 2007, 418 (2): 165–9. PMID 17398001. S2CID 25453633. doi:10.1016/j.neulet.2007.03.033.
- ^ Intracellular Mechanisms of Inflammation:PDE4 Promotes the Release of Proinflammatory Mediators. Celgene Corporation. 2012 [2012-07-24]. (原始內容存檔於2019-08-13).
- ^ Maxwell CR, Kanes SJ, Abel T, Siegel SJ. Phosphodiesterase inhibitors: a novel mechanism for receptor-independent antipsychotic medications. Neuroscience. 2004, 129 (1): 101–7. PMID 15489033. S2CID 19578277. doi:10.1016/j.neuroscience.2004.07.038.
- ^ Kanes SJ, Tokarczyk J, Siegel SJ, Bilker W, Abel T, Kelly MP. Rolipram: A specific phosphodiesterase 4 inhibitor with potential antipsychotic activity. Neuroscience. 2006, 144 (1): 239–246. PMC 3313447 . PMID 17081698. doi:10.1016/j.neuroscience.2006.09.026.
- ^ Beal, MF; Cleren, C; Calingasan, NY; Yang, L; Klivenyi, P; Lorenzl, S. Oxidative Damage in Parkinson's Disease. U.S. Army Medical Research and Material Command Fort Detrick, Maryland 21702-5012. 2005. (原始內容存檔於May 23, 2012).
- ^ Smith, DL; Pozueta, J; Gong, B; Arancio, O; Shelanski, M. Reversal of long-term dendritic spine alterations in Alzheimer disease models. Proceedings of the National Academy of Sciences of the United States of America. September 2009, 106 (39): 16877–16882. Bibcode:2009PNAS..10616877S. PMC 2743726 . PMID 19805389. doi:10.1073/pnas.0908706106 .
- ^ Dinter, H. Phosphodiesterase type 4 inhibitors: potential in the treatment of multiple sclerosis?. BioDrugs. February 2000, 13 (2): 87–94. PMID 18034515. S2CID 23444101. doi:10.2165/00063030-200013020-00002.
- ^ Dyke, HJ; Montana, JG. Update on the therapeutic potential of PDE4 inhibitors. Expert Opinion on Investigational Drugs. January 2002, 11 (1): 1–13. PMID 11772317. S2CID 22623399. doi:10.1517/13543784.11.1.1.
- ^ DALIRESP (roflumilast) tablet [Forest Laboratories, Inc.]. DailyMed. Forest Laboratories, Inc. August 2013 [13 November 2013]. (原始內容存檔於2014-09-15).
- ^ Yu, M. C.; Chen, J. H.; Lai, C. Y.; Han, C. Y.; Ko, W. C. Luteolin, a non-selective competitive inhibitor of phosphodiesterases 1-5, displaced [(3)H]-rolipram from high-affinity rolipram binding sites and reversed xylazine/ketamine-induced anesthesia. European Journal of Pharmacology. 2009, 627 (1–3): 269–275. PMID 19853596. doi:10.1016/j.ejphar.2009.10.031.
- ^ Brooks, M. FDA Clears Apremilast (Otezla) for Psoriatic Arthritis. Medscape Medical News (WebMD). 21 March 2014 [28 March 2014]. (原始內容存檔於2023-07-02).
- ^ Lowes, R. FDA Approves Apremilast (Otezla) for Plaque Psoriasis. Medscape Medical News (WebMD). 23 September 2014 [13 October 2014]. (原始內容存檔於2023-07-02).
- ^ Rennard, S; Knobil, K; Rabe, KF; Morris, A; Schachter, N; Locantore, N; Canonica, WG; Zhu, Y; Barnhart, F. The efficacy and safety of cilomilast in COPD. Drugs. 2008, 68 (Suppl 2): 3–57. PMID 19105585. S2CID 2216800. doi:10.2165/0003495-200868002-00002.
- ^ Nazarian, R; Weinberg, JM. AN-2728, a PDE4 Inhibitor for the Potential Topical Treatment of Psoriasis and Atopic Dermatitis. Current Opinion in Investigational Drugs. November 2009, 10 (11): 1236–42. PMID 19876791.
- ^ Moustafa, F; Feldman, SR. A Review of Phosphodiesterase-Inhibition and the Potential Role for Phosphodiesterase 4-Inhibitors in Clinical Dermatology (PDF). Dermatology Online Journal. 16 May 2014, 20 (5): 22608 [2024-01-30]. PMID 24852768. doi:10.5070/D3205022608 . (原始內容存檔 (PDF)於2017-10-05).
- ^ FDA Approves Eucrisa for Eczema. U.S. Food and Drug Administration. 14 December 2016 [2024-01-30]. (原始內容存檔於2019-04-23).
- ^ 28.0 28.1 Boswell-Smith, Victoria; Spina, Domenico; Page, Clive P. Phosphodiesterase inhibitors. British Journal of Pharmacology. January 2006, 147 (Suppl 1): S252–257. ISSN 0007-1188. PMC 1760738 . PMID 16402111. doi:10.1038/sj.bjp.0706495.
- ^ Collado, M. C.; Beleta, J.; Martinez, E.; Miralpeix, M.; Domènech, T.; Palacios, J. M.; Hernández, J. Functional and biochemical evidence for diazepam as a cyclic nucleotide phosphodiesterase type 4 inhibitor. British Journal of Pharmacology. 1998, 123 (6): 1047–1054. PMC 1565256 . PMID 9559885. doi:10.1038/sj.bjp.0701698.
- ^ de Visser, Y. P.; Walther, F. J.; Laghmani E. H.; van Wijngaarden, S.; Nieuwland, K.; Wagenaar, G. T. Phosphodiesterase-4 inhibition attenuates pulmonary inflammation in neonatal lung injury. European Respiratory Journal. 2008, 31 (3): 633–644. PMID 18094015. doi:10.1183/09031936.00071307 .
- ^ FDA Approves Arcutis' Zoryve (Roflumilast) Cream 0.3% For the Treatment of Plaque Psoriasis in Individuals Age 12 and Older (新聞稿). Arcutis Biotherapeutics. 29 July 2022 [1 August 2022]. (原始內容存檔於1 August 2022).