西咪替丁：修订间差异

'''西咪替丁'''（[[国际非专利药品名称|INN]]：cimetidine），也称'''甲氰咪胍'''、'''西米替丁'''或'''希美得定'''，商品名稱為'''泰胃美'''（'''Tagamet'''），是一種[[组胺]][[H2受体阻抗剂|H₂受体阻抗剂]]，主要用於抑制[[胃酸]]的分泌<ref name="Elks2014">{{Cite book||title=The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies|last=Elks|first=J.|date=2014-11-14|publisher=Springer|isbn=978-1-4757-2085-3|pages=275–|access-date=2018-09-02|||}}</ref><ref name="IndexNominum2000">{{Cite book||title=Index Nominum 2000: International Drug Directory|date=January 2000|publisher=Taylor & Francis|isbn=978-3-88763-075-1|pages=234–|access-date=2018-09-02|||}}</ref><ref name="MortonMorton1999">{{Cite book||title=Concise Dictionary of Pharmacological Agents: Properties and Synonyms|last=Morton|first=Ian|last2=Morton|first2=I. K.|last3=Hall|first3=Judith M.|date=1999-10-31|publisher=Springer Science & Business Media|isbn=978-0-7514-0499-9|pages=77–}}</ref>，並用于治疗[[胃灼热]]和[[消化道溃疡]]。<ref name="BurchumRosenthal2014">{{Cite book||title=Lehne's Pharmacology for Nursing Care|last=Burchum|first=Jacqueline|last2=Rosenthal|first2=Laura|date=2014-12-02|publisher=Elsevier Health Sciences|isbn=978-0-323-34026-7|pages=952–}}</ref>在[[英国]]，西咪替丁可以作為非處方藥出售给公众（以2周的用量為限），用于16岁以上的成人和儿童短期舒緩[[胃痛]]、[[消化不良]]、[[胃酸]]过多的症状（每次最大用量为200毫克；每天不可用多於800毫克），或用于预防夜间[[胃灼热]]（每晚用量100毫克）。<ref>{{Cite web|url=https://bnf.nice.org.uk/drug/cimetidine.html#exceptionsToLegalCategory|title=CIMETIDINE|last=BNF}}</ref>

西咪替丁在1971年首次發現，並在1977年投入市場。<ref name="FischerGanellin2010">{{Cite book||title=Analogue-based Drug Discovery II|last=Fischer|first=Janos|last2=Ganellin|first2=C. Robin|date=2010-08-24|publisher=John Wiley & Sons|isbn=978-3-527-63212-1|pages=4|access-date=2018-09-02|||}}</ref><ref>{{Cite book||title=Analogue-based Drug Discovery|last=Fischer|first=Janos|last2=Ganellin|first2=C. Robin|date=2006|publisher=John Wiley & Sons|isbn=9783527607495|page=444|language=en|access-date=2018-09-02|||}}</ref>西咪替丁在1976年批准在[[英国]]上市，并在1979年由[[美国食品药品监督管理局]]批准在美国作為处方藥出售。

有些证据表示西咪替丁可能對治療尋常[[疣]]有效；但在更严格的[[双盲]][[临床试验]]中，西咪替丁並不比[[安慰剂]]有效。<ref>{{Cite journal|title=Use of histamine2-antagonists for the treatment of verruca vulgaris|date=July 2007|journal=The Annals of Pharmacotherapy|issue=7|doi=10.1345/aph.1H616|volume=41|pages=1222–6|pmid=17535844}}</ref><ref>{{Cite journal|title=Cimetidine therapy for recalcitrant warts in adults|date=June 1996|journal=Archives of Dermatology|issue=6|doi=10.1001/archderm.1996.03890300108014|volume=132|pages=680–2|pmid=8651718}}</ref><ref>{{Cite journal|title=Is cimetidine effective for nongenital warts: a double-blind, placebo-controlled study|date=April 1997|journal=Archives of Dermatology|issue=4|doi=10.1001/archderm.133.4.533|volume=133|pages=533–4|pmid=9126017}}</ref>

西咪替丁能抑制{{Tsl|en|Aminolevulinic_acid_synthase|ALA合成酶}}的活性，因此，西咪替丁在预防和治疗[[紫質症]]的急性病發中可能有某些价值。<ref>{{Cite book|url=https://www.ncbi.nlm.nih.gov/books/NBK1193/|title=Acute Intermittent Porphyria|last=Whatley|first=SD|last2=Badminton|first2=MN|last3=Pagon|first3=RA|last4=Adam|first4=MP|last5=Ardinger|first5=HH|last6=Wallace|first6=SE|last7=Amemiya|first7=A|last8=Bean|first8=LJH|last9=Bird|first9=TD|date=2013|pmid=20301372}}</ref><ref>{{Cite book|url=http://fpm.anzca.edu.au/documents/apmse4_2015_final|title=Acute Pain Management: Scientific Evidence|last=Schug, SA; Palmer, GM; Scott, DA; Halliwell, R; Trinca, J; APM:SE Working Group of the Australian and New Zealand College of Anaesthetists and Faculty of Pain Medicine|date=2015|publisher=Australian and New Zealand College of Anaesthetists and Faculty of Pain Medicine|accessdate=2017-09-07|isbn=978-0-9873236-6-8|edition=4th|location=Melbourne, Australia|page=316|format=PDF|||}}</ref>

西咪替丁的已知[[副作用]]包括輕微和短暫的[[腹瀉]]、[[皮疹]]、[[頭暈]]、[[疲勞]]、[[便秘]]和[[肌肉疼痛]]。<ref name="RitterLewis2008">{{Cite book||title=A Textbook of Clinical Pharmacology and Therapeutics|last=Ritter|first=James|last2=Lewis|first2=Lionel|last3=Mant|first3=Timothy|last4=Ferro|first4=Albert|date=2008-04-25|publisher=CRC Press|isbn=978-1-4441-1300-6|edition=5|pages=250–}}</ref>有报告指老年人服用後可能发生[[譫妄]]。<ref name="RitterLewis2008"/>由於其[[激素]]作用，西咪替丁在長期治療期間罕見地導致男性[[性功能障礙]]，包括[[性慾減退]]、[[勃起功能障礙]]以及[[男性乳房發育症]]（0.1-0.2％）。<ref name="RitterLewis2008"/><ref>{{Cite journal|title=Cimetidine: adverse reactions and acute toxicity|date=February 1981|journal=American Journal of Hospital Pharmacy|issue=2|volume=38|pages=188–97|pmid=7011006}}</ref><ref>{{Cite journal|title=Safety issues relating to long-term treatment with histamine H2-receptor antagonists|journal=Alimentary Pharmacology & Therapeutics|doi=10.1111/j.1365-2036.1993.tb00597.x|year=1993|volume=7 Suppl 2|pages=35–40|pmid=8103374}}</ref>[[间质性肾炎]]、[[荨麻疹]]、[[血管性水肿]]也可能罕見地發生。<ref name="RitterLewis2008" />西咪替丁也与短暫[[氨基转移酶]]活动上升有關，但{{tsl|en|Hepatotoxicity|肝中毒}}是罕见的。<ref name="Kelly2009" />

* 西咪替丁影響[[美沙酮]]的代謝，有時導致血液濃度上升和更多的副作用，並且可能與抗[[瘧疾]]藥物[[羥氯喹]]相互作用。<ref>{{Cite journal|title=Pharmacokinetics of hydroxychloroquine and chloroquine during treatment of rheumatic diseases|date=June 1996|journal=Lupus|doi=10.1177/096120339600500104|volume=5 Suppl 1|pages=S11-5|pmid=8803904}}</ref>

* 給予西咪替丁後，[[佐米曲普坦]]及其活性代謝物的[[消除半衰期]]和{{tsl|en|Area_under_the_curve_(pharmacokinetics)|曲线下面積}}大約增加了一倍。<ref>See complete drug interactions for Zomig (zolmitriptan succinate used for migraine relief) in package insert: {{Cite web|url=http://www1.astrazeneca-us.com/pi/Zomig.pdf|title=Highlights of Zomig Prescribing Information|publisher=AstraZeneca|access-date=2018-09-02|||}}</ref>

* 西咪替丁是管狀[[肌酸酐]]分泌的強抑製劑。 肌酐是[[肌酸]]分解的副產物，而肌酐的累積與[[尿毒症]]有關 ，但肌酐累積的症狀尚不清楚，因為它們難以與其他含氮廢物堆積物分離。<ref>{{Cite journal|title=Transcellular transport of creatinine in renal tubular epithelial cell line LLC-PK1|date=June 2005|journal=Drug Metabolism and Pharmacokinetics|issue=3|doi=10.2133/dmpk.20.200|volume=20|pages=200–5|pmid=15988122}}</ref>

* 西咪替丁降低作為[[前體藥物]]的CYP2D6受質的作用，例如[[可待因]]、[[曲馬多]]和[[他莫昔芬]]。<ref name="FullerSajatovic2005">{{Cite book||title=Drug Information Handbook for Psychiatry|last=Fuller|first=Matthew A.|last2=Sajatovic|first2=Martha|publisher=Lexi-Comp|year=2005|page=285|access-date=2018-09-02|||}}</ref>

西咪替丁是某些[[細胞色素P450]]酶的有效抑制劑，<ref name="Dart2004">{{Cite book||title=Medical Toxicology|last=Dart|first=Richard C.|publisher=Lippincott Williams & Wilkins|year=2004|isbn=978-0-7817-2845-4|pages=402–|access-date=2018-09-02|||}}</ref><ref name="LemkeWilliams2008">{{Cite book||title=Foye's Principles of Medicinal Chemistry|last=Lemke|first=Thomas L.|last2=Williams|first2=David A.|publisher=Lippincott Williams & Wilkins|year=2008|isbn=978-0-7817-6879-5|pages=273–}}</ref>其中包括[[CYP1A2]]、[[CYP2C9]]、[[CYP2C19]]、[[CYP2D6]]、{{tsl|en|CYP2E1}}和[[CYP3A4]]。<ref name="KarallieddeClarke2010">{{Cite book||title=Adverse Drug Interactions: A Handbook for Prescribers|last=Karalliedde|first=Lakshman Delgoda|last2=Clarke|first2=Simon F.J.|last3=Collignon|first3=Ursula|last4=Karalliedde|first4=Janaka|date=2010-01-29|publisher=CRC Press|isbn=978-0-340-92769-4|pages=633–|access-date=2018-09-02|||}}</ref>西咪替丁似乎主要是CYP1A2、CYP2D6和CYP3A4<ref name="PriskornLarsen1997">{{Cite journal|title=Pharmacokinetic interaction study of citalopram and cimetidine in healthy subjects|journal=European Journal of Clinical Pharmacology|issue=3|doi=10.1007/s002280050282|year=1997|volume=52|pages=241–2|pmid=9218934}}</ref>的中度抑制剂。<ref name="VallerandSanoski2016">{{Cite book||title=Davis's Drug Guide for Nurses|last=Vallerand|first=April Hazard|last2=Sanoski|first2=Cynthia A|last3=Deglin|first3=Judith Hopfer|date=2016-05-25|publisher=F.A. Davis|isbn=978-0-8036-5779-3|pages=636–}}</ref>這是值得注意的，因為這三種CYP450[[同工酶]]參與CYP450介導的[[生物轉化作用]]。<ref name="MartinezAlbet1999">{{Cite journal|title=Comparative in vitro and in vivo inhibition of cytochrome P450 CYP1A2, CYP2D6, and CYP3A by H2-receptor antagonists||date=April 1999|journal=Clinical Pharmacology and Therapeutics|issue=4|doi=10.1016/S0009-9236(99)70129-3|volume=65|pages=369–76|pmid=10223772}}</ref>然而，CYP1A2、CYP2C9、CYP2C19、CYP2D6、CYP2E1和CYP3A4也牽涉在許多常用藥物的氧化[[代謝]]中。<ref name="Delafuente2003">{{Cite journal|title=Understanding and preventing drug interactions in elderly patients|date=November 2003|journal=Critical Reviews in Oncology/Hematology|issue=2|doi=10.1016/j.critrevonc.2003.04.004|volume=48|pages=133–43|pmid=14607376}}</ref>因此西咪替丁與其他藥物一起服用時，可能會產生許多[[药物相互作用]]。

西咪替丁已知是幾種CYP450酶的可逆性和[[競爭性抑制劑]]，<ref name="Kelly2009">{{Cite book||title=Diseases of the Liver and Biliary System in Children|last=Kelly|first=Deirdre|date=2009-01-26|publisher=John Wiley & Sons|isbn=978-1-4443-0054-3|pages=224–}}</ref><ref name="RosenfeldLoose2007">{{Cite book||title=Pharmacology|last=Rosenfeld|first=Gary C.|last2=Loose|first2=David S.|publisher=Lippincott Williams & Wilkins|year=2007|isbn=978-0-7817-8074-2|pages=202–}}</ref><ref name="Cairns2012">{{Cite book||title=Essentials of Pharmaceutical Chemistry|last=Cairns|first=Donald|publisher=Pharmaceutical Press|year=2012|isbn=978-0-85369-979-8|pages=110–}}</ref>也是CYP2D6的{{link-en|自殺型抑制劑|Suicide inhibition}}，可造成不可逆的抑制。<ref name="Zhou2016">{{Cite book||title=Cytochrome P450 2D6: Structure, Function, Regulation and Polymorphism|last=Shufeng Zhou|date=2016-04-06|publisher=CRC Press|isbn=978-1-4665-9788-4|pages=299–}}</ref>西咪替丁[[咪唑]]環的[[氮]]原子能直接與[[活性位點]]的絡合[[血紅素]][[鐵]]結合，從而可逆地抑制CYP450酶，阻斷其他藥物的氧化。<ref name="pmid9630736">{{Cite journal|title=The detoxification enzyme systems|date=June 1998|journal=Alternative Medicine Review|issue=3|volume=3|pages=187–98|pmid=9630736}}</ref>

已知高劑量西咪替丁具有弱的[[抗雄激素]]活性。<ref name="Becker2001">{{Cite book||title=Principles and Practice of Endocrinology and Metabolism|last=Becker|first=Kenneth L.|publisher=Lippincott Williams & Wilkins|year=2001|isbn=978-0-7817-1750-2|pages=1196–|access-date=2018-09-02|||}}</ref><ref name="pmid6150641">{{Cite journal|title=Comparison of the effectiveness of ranitidine and cimetidine in inhibiting acid secretion in patients with gastric hypersecretory states|date=November 1984|journal=The American Journal of Medicine|issue=5B|volume=77|pages=90–105|pmid=6150641}}</ref><ref name="pmid3921876">{{Cite journal|title=[Dysfunction of the hypothalamo-hypophyseal-gonadal axis induced by histamine H2 antagonists. Review of the literature and personal observations]|date=March 1985|journal=Minerva Medica|issue=12|volume=76|pages=579–86|language=it|pmid=3921876}}</ref>它作為[[受體拮抗劑]]，可以直接和競爭性地結合[[雄激素受體]]，以阻斷[[睪酮]]與[[二氫睪酮]]等雄激素的作用。<ref name="pmid428705">{{Cite journal|title=Cimetidine is an antiandrogen in the rat||date=March 1979|journal=Gastroenterology|issue=3|volume=76|pages=504–8|pmid=428705}}</ref><ref name="pmid6123322">{{Cite journal|title=The effects of histamine H2 receptor antagonists on androgen action in vivo and dihydrotestosterone binding to the rat prostate androgen receptor in vitro|url=http://linkinghub.elsevier.com/retrieve/pii/0006-2952(82)90449-X|date=March 1982|journal=Biochemical Pharmacology|issue=5|doi=10.1016/0006-2952(82)90449-X|volume=31|pages=677–84|pmid=6123322|access-date=2018-09-02|||}}</ref>然而西咪替丁對雄激素受體的[[親和力]]非常弱。根據一項研究所示，它對人雄激素受體的親和力僅有人工合成[[同化激素]]{{tsl|en|metribolone|甲基群勃龙}}的0.00084%。<ref name="pmid6725525">{{Cite journal|title=The use of human skin fibroblasts to obtain potency estimates of drug binding to androgen receptors|date=July 1984|journal=J. Clin. Endocrinol. Metab.|issue=1|doi=10.1210/jcem-59-1-51|volume=59|pages=51–5|pmid=6725525}}</ref>無論如何，在足夠高的劑量下，西咪替丁在動物體內表現出微弱但顯著的抗雄激素作用，包括[[大鼠]]腹側[[前列腺]]和[[小鼠]][[腎臟]]的抗雄激素作用；大鼠上如[[前列腺]]和[[精囊]]等{{tsl|en|male accessory glands|雄性附屬腺體}}質量減少；和雄性大鼠中{{tsl|en|Gonadotropin|促性腺激素}}水平升高（由於雄激素對HPG軸的[[負反饋]]減少）。<ref name="GerallMoltz2013" /><ref name="PlessisAgarwal2014">{{cite book|author1=Stefan S. du Plessis|author2=Ashok Agarwal|author3=Edmund S. Sabanegh, Jr.|title=Male Infertility: A Complete Guide to Lifestyle and Environmental Factors||date=2014-07-26|publisher=Springer|isbn=978-1-4939-1040-3|pages=233–}}</ref>除了雄激素受體拮抗作用外，已知西咪替丁能通過抑制參與雌二醇代謝失活的CYP450酶，從而抑制[[雌二醇]]的2-[[羥基]]化，導致[[雌激素]]水平增加。<ref name="pmid2747769">{{cite journal | vauthors = Galbraith RA, Michnovicz JJ | title = The effects of cimetidine on the oxidative metabolism of estradiol | journal = The New England Journal of Medicine | volume = 321 | issue = 5 | pages = 269–74 | date = August 1989 | pmid = 2747769 | doi = 10.1056/NEJM198908033210501 | url = http://www.nejm.org/doi/abs/10.1056/NEJM198908033210501?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%3dpubmed }}</ref><ref name="pmid1988774">{{cite journal | vauthors = Michnovicz JJ, Galbraith RA | title = Cimetidine inhibits catechol estrogen metabolism in women | journal = Metabolism | volume = 40 | issue = 2 | pages = 170–4 | date = February 1991 | pmid = 1988774 | doi = 10.1016/0026-0495(91)90169-W }}</ref><ref name="PescovitzWalvoord2007">{{cite book | first1 = Ora H. | last1 = Pescovitz | first2 = Emily C. | last2 = Walvoord | name-list-format = vanc | title = When Puberty is Precocious: Scientific and Clinical Aspects | | date = 2007-06-06 | publisher = Springer Science & Business Media | isbn = 978-1-59745-499-5 | pages = 203– }}</ref><ref name="PolatCuhaci2014">{{cite journal | vauthors = Cuhaci N, Polat SB, Evranos B, Ersoy R, Cakir B | title = Gynecomastia: Clinical evaluation and management | journal = Indian Journal of Endocrinology and Metabolism | volume = 18 | issue = 2 | pages = 150–8 | date = March 2014 | pmid = 24741509 | doi = 10.4103/2230-8210.129104 | pmc=3987263}}</ref><ref name="RendicCarlo2010">{{cite journal | vauthors = Rendic S, Di Carlo FJ | title = Human cytochrome P450 enzymes: a status report summarizing their reactions, substrates, inducers, and inhibitors | journal = Drug Metabolism Reviews | volume = 29 | issue = 1-2 | pages = 413–580 | year = 2010 | pmid = 9187528 | doi = 10.3109/03602539709037591 }}</ref><ref name="GalbraithMichnovicz1989">{{cite journal | vauthors = Galbraith RA, Michnovicz JJ | title = The effects of cimetidine on the oxidative metabolism of estradiol | journal = The New England Journal of Medicine | volume = 321 | issue = 5 | pages = 269–74 | date = August 1989 | pmid = 2747769 | doi = 10.1056/NEJM198908033210501 }}</ref>有報告指，西咪替丁可以減少[[睾酮]]合成，並增加[[催乳素]]水平，這可能是[[雌激素]]水平上升的繼發性因素。<ref name="pmid22862307">{{cite journal | vauthors = Deepinder F, Braunstein GD | title = Drug-induced gynecomastia: an evidence-based review | journal = Expert Opin Drug Saf | volume = 11 | issue = 5 | pages = 779–95 | date = September 2012 | pmid = 22862307 | doi = 10.1517/14740338.2012.712109 | url = }}</ref>

在用於治療的濃度下，西咪替丁對男性的循環內睾酮濃度沒有影響或僅有輕微上升<ref name="GerallMoltz2013" />，睾酮水平的增加可能是因為雄激素受體拮抗作用，造成{{link-en|HPG軸|Hypothalamic–pituitary–gonadal axis}}上的[[負反饋]]機制的喪失。<ref name="GerallMoltz2013" /><ref name="PlessisAgarwal2014" />在典型用於治療消化性潰瘍的臨床劑量下，西咪替丁所引致的[[男性乳房發育症]]的發生率低於1%。<ref name="GerallMoltz2013">{{cite book|author1=Arnold A. Gerall|author2=Howard Moltz|author3=Ingeborg L. Ward|title=Sexual Differentiation||date=2013-11-11|publisher=Springer Science & Business Media|isbn=978-1-4899-2453-7|pages=207–}}</ref><ref name="WattsFaingold2009">{{cite book|author1=Stephanie Watts|author2=Carl Faingold|author3=George Dunaway|author4=Lynn Crespo|title=Brody's Human Pharmacology - E-Book||date=2009-04-01|publisher=Elsevier Health Sciences|isbn=0-323-07575-4|pages=472–}}</ref>在一項對超過9,000名服用西咪替丁的患者進行的調查中，男性乳房發育症是最常見的[[內分泌]]相關副作用，但僅有0.2%的患者報告自己受該副作用影響。<ref name="GerallMoltz2013" />但在用於治療{{tsl|en|Zollinger–Ellison_syndrome|佐埃二氏症}}的高劑量時，西咪替丁可能有更高的男性乳房發育症發病率。<ref name="WattsFaingold2009" />在一項小型研究中，在25名接受每天1600mg西咪替丁治療的男性十二指腸潰瘍患者中，他們的男性乳房發育症發病率為20%。<ref name="pmid22862307" />症狀在治療4個月後出現，並在停用西咪替丁後一個月內消退。<ref name="pmid22862307" />在另一項小型研究中，在接受過西咪替丁治療的22名男性中，有60%病人患有由西咪替丁引起的[[乳房]]病變和[[勃起功能障礙]]。<ref name="pmid22862307" />當病人轉用[[雷尼替丁]]時，這些不良反應都得到徹底解決。<ref name="pmid22862307" />對包含超過80,000名男性的[[英國]]{{tsl|en|Clinical Practice Research Datalink#General Practice Research Database|全科醫學研究數據庫}}進行的一項研究發現，與非使用者相比，西咪替丁使用者中男性乳房發育症的相對風險為7.2；<ref name="pmid22862307" />而在服用西咪替丁大於或等於1,000毫克的男性當中，男性乳房發育症的風險是非使用者的40倍以上。<ref name="pmid22862307" />病人在連續用藥後7至12個月期間風險最高。<ref name="pmid22862307" />與西咪替丁相關的男性乳房發育症可歸因於乳房組織中雄激素受體的拮抗，導致雌激素在乳房組織中的作用不受雄激素的影響，雖然因代謝遭抑制而增加的雌激素水平也是可能的機制。<ref name="pmid22862307" />在一些研究中，西咪替丁還與男性的{{tsl|en|Oligospermia|少精子症}}和[[性功能障礙]]有關。<ref name="GerallMoltz2013" /><ref name="PlessisAgarwal2014" /><ref name="pmid22862307" />

雖然只被FDA批准用於抑制胃酸分泌，西咪替丁已被提倡用於許多的皮膚病中。<ref>{{Cite journal|title=Cimetidine: a review of the recent developments and reports in cutaneous medicine|date=March 2003|journal=Dermatology Online Journal|issue=2|volume=9|pages=4|pmid=12639457}}</ref>西咪替丁是典型的组胺[[H2受体阻抗剂|H₂受体阻抗剂]]，並且是其他H₂受體阻抗劑的原型。西咪替丁是由[[詹姆士·W·布拉克]]、{{tsl|en|C. Robin Ganellin}}等人在現為[[葛蘭素史克]]的SK&F實驗室的研發成果。<ref name="ACS Landmarks">{{Cite web|url=http://portal.acs.org/portal/PublicWebSite/education/whatischemistry/landmarks/cimetidinetagamet/|title=Tagamet^®: Discovery of Histamine H₂-receptor Antagonists|accessdate=2012-06-25|work=National Historic Chemical Landmarks|publisher=American Chemical Society|||}}</ref>這是使用理性[[藥物設計]]方法發現的首批藥物。[[詹姆士·W·布拉克]]爵士因發現[[普萘洛爾]]與西咪替丁而獲得1988年的[[諾貝爾生理學或醫學獎]]。

早在1964年，人們就知道[[組織胺]]會促進胃酸的分泌，但傳統的抗組織胺藥物對胃酸分泌沒有影響。SK&F的科學家因而假設有兩個組織胺受體的存在。H₁是傳統的組織胺受體；H₂為刺激胃酸分泌的組織胺受體。SK&F團隊用組織胺的結構進行一系列的設計。合成了數百個修飾過的化合物，試圖阻斷這個完全未知的H₂受體上。第一个突破是N^α-脒基组胺，為不完全的H₂受體阻抗劑。而後又根據此物重新定義受體且合成出{{le|布立馬胺|burimamide}}，比N^α-脒基组胺強100倍且是一個H₂受體的[[競爭性拮抗劑]]，從此證實了H₂受體的存在。

西咪替丁於1976年首次在[[英國]]上市，1977年8月在美国上市；因此，從開始研發H₂受體阻抗劑起，就花了12年才開始商業化。到1979年，西咪替丁已在100多個國家上市，成為美國，[[加拿大]]和其他幾個國家最暢銷的處方藥。1997年11月，[[美國化學學會]]和[[英國皇家化學學會]]在英國[[哈洛]]的SmithKline Beecham研究設施揭幕儀式上，將西咪替丁的成功研發稱為藥物史上重要的一頁，並將其歸為其中一項國際化學史里程碑（International Historic Chemical Landmark）。<ref name="Freemantle">{{Cite web|url=http://pubs.acs.org/cen/coverstory/83/8325/8325tagamet.html|title=Tagamet|accessdate=2013-07-01|last=Fremantle|first=Michael|work=Chemical and Engineering news|||}}</ref>

西咪替丁的商品名稱Tagamet是antagonist和cimetidine兩詞的[[混成詞]]。<ref name="ACS Landmarks"/>在西咪替丁引入美國市場後，又有[[雷尼替丁]]和[[法莫替丁]]這兩種H₂受體阻抗劑被批准。西咪替丁成為有史以來第一種每年銷售額超過10億美元的藥物。<ref>{{Cite news|url=http://www.guernicamag.com/features/111/me_too_drugs/|title=Pharmaceutical Sales 101: Me-Too Drugs|last=Whitney|first=Jake|date=February 2006|work=[[Guernica Magazine|Guernica]]|accessdate=2008-07-31|||}}</ref>

西咪替丁現已在很大程度上被[[質子泵抑製劑]]所取代；但在許多國家，西咪替丁都可以作為治療[[胃灼熱]]的[[非處方藥]]使用。<ref name="Freemantle"/>

* Tagamet^®: Discovery of Histamine H₂-receptor Antagonists [[美国化学学会]] 國家歷史化學地標