| 词条 | Mestranol |
| 释义 |
| Verifiedfields = verified | Watchedfields = verified | verifiedrevid = 462249106 | IUPAC_name = (8R,9S,13S,14S,17R)-17-ethynyl-3-methoxy-13-methyl-7,8,9,11,12,14,15,16-octahydro-6H-cyclopenta[a]phenanthren-17-ol | image = Mestranol.svg | width = 225px | image2 = Mestranol molecule ball.png | width2 = 250px | tradename = Enovid, Norinyl, Ortho-Novum, others | Drugs.com = {{drugs.com|international|mestranol}} | MedlinePlus = a601050 | pregnancy_AU = | pregnancy_US = | pregnancy_category = | legal_AU = | legal_UK = | legal_US = | legal_status = Rx-only | routes_of_administration = By mouth[1] | class = Estrogen; Estrogen ether | bioavailability = | protein_bound = | metabolism = | elimination_half-life = | excretion = | CAS_number_Ref = {{cascite|correct|??}} | CAS_number = 72-33-3 | ATC_prefix = None | ATC_suffix = | ATC_supplemental = | PubChem = 6291 | IUPHAR_ligand = 7087 | DrugBank_Ref = {{drugbankcite|correct|drugbank}} | DrugBank = DB01357 | ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} | ChemSpiderID = 6054 | UNII_Ref = {{fdacite|correct|FDA}} | UNII = B2V233XGE7 | KEGG_Ref = {{keggcite|correct|kegg}} | KEGG = D00575 | ChEBI_Ref = {{ebicite|correct|EBI}} | ChEBI = 6784 | ChEMBL_Ref = {{ebicite|correct|EBI}} | ChEMBL = 1201151 | synonyms = Ethinylestradiol 3-methyl ether; EEME; EE3ME; CB-8027; L-33355; RS-1044; 17α-Ethynylestradiol 3-methyl ether; 17α-Ethynyl-3-methoxyestra-1,3,5(10)-trien-17β-ol; 3-Methoxy-19-norpregna-1,3,5(10)-trien-20-yn-17α-ol | C=21 | H=26 | O=2 | molecular_weight = 310.437 g/mol | SMILES = O(c1cc4c(cc1)[C@H]3CC[C@]2([C@@H](CC[C@]2(C#C)O)[C@@H]3CC4)C)C | StdInChI_Ref = {{stdinchicite|correct|chemspider}} | StdInChI = 1S/C21H26O2/c1-4-21(22)12-10-19-18-7-5-14-13-15(23-3)6-8-16(14)17(18)9-11-20(19,21)2/h1,6,8,13,17-19,22H,5,7,9-12H2,2-3H3/t17-,18-,19+,20+,21+/m1/s1 | StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} | StdInChIKey = IMSSROKUHAOUJS-MJCUULBUSA-N }}Mestranol, sold under the brand names Enovid, Norinyl, and Ortho-Novum among others, is an estrogen medication which has been used in birth control pills, menopausal hormone therapy, and the treatment of menstrual disorders.[1][3][4][5] It is formulated in combination with a progestin and is not available alone.[5] It is taken by mouth.[1]Side effects of mestranol include nausea, breast tension, edema, and breakthrough bleeding among others.[1] It is an estrogen, or an agonist of the estrogen receptors, the biological target of estrogens like estradiol.[2] Mestranol is a prodrug of ethinylestradiol in the body.[2] Mestranol was discovered in 1956 and was introduced for medical use in 1957.[11][12] It was the estrogen component in the first birth control pill.[11][12] In 1969, mestranol was replaced by ethinylestradiol in most birth control pills, although mestranol continues to be used in a few birth control pills even today.[15][5] Mestranol remains available only in a few countries, including the United States, United Kingdom, Japan, and Chile.[5] Medical usesMestranol was employed as the estrogen component in many of the first oral contraceptives, such as mestranol/noretynodrel (brand name Enovid) and mestranol/norethisterone (brand names Ortho-Novum, Norinyl), and is still in use today.[3][4][5] In addition to its use as an oral contraceptive, mestranol has been used as a component of menopausal hormone therapy for the treatment of menopausal symptoms.[1] Side effects{{See also|Ethinylestradiol#Side effects|Estrogen (medication)#Side effects}}PharmacologyMestranol is a biologically inactive prodrug of ethinylestradiol to which it is demethylated in the liver with a conversion efficiency of 70% (50 µg of mestranol is pharmacokinetically bioequivalent to 35 µg of ethinylestradiol, or ethinylestradiol being about 1.7 times as orally potent by weight as mestranol).[5][6][7] It has been found to possess 0.1 to 2.3% of the relative binding affinity of estradiol (100%) for the estrogen receptor, compared to 75 to 190% for ethinylestradiol.[8][9] The effective ovulation-inhibiting dosage of mestranol has been studied.[10][11] {{Oral potencies of estrogens}}Chemistry{{See also|List of estrogens|List of estrogen esters#Ethers of steroidal estrogens}}Mestranol, also known as ethinylestradiol 3-methyl ether (EEME) or as 17α-ethynyl-3-methoxyestra-1,3,5(10)-trien-17β-ol, is a synthetic estrane steroid and a derivative of estradiol.[29][30][12] It is specifically a derivative of ethinylestradiol (17α-ethynylestradiol) with a methyl ether at the C3 position.[29][30] HistoryIn April 1956, noretynodrel was investigated, in Puerto Rico, in the first large-scale clinical trial of a progestogen as an oral contraceptive.[13][14] The trial was conducted in Puerto Rico due to the high birth rate in the country and concerns of moral censure in the United States.[15] It was discovered early into the study that the initial chemical syntheses of noretynodrel had been contaminated with small amounts (1–2%) of the 3-methyl ether of ethinylestradiol (noretynodrel having been synthesized from ethinylestradiol).[13][14] When this impurity was removed, higher rates of breakthrough bleeding occurred.[13][14] As a result, mestranol, that same year (1956),[16] was developed and serendipitously identified as a very potent synthetic estrogen (and eventually as a prodrug of ethinylestradiol), given its name, and added back to the formulation.[13][14] This resulted in Enovid by G. D. Searle & Company, the first oral contraceptive and a combination of 9.85 mg noretynodrel and 150 μg mestranol per pill.[13][14] Around 1969, mestranol was replaced by ethinylestradiol in most combined oral contraceptives due to widespread panic about the recently uncovered increased risk of venous thromboembolism with estrogen-containing oral contraceptives.[17] The rationale was that ethinylestradiol was approximately twice as potent by weight as mestranol and hence that the dose could be halved, which it was thought might result in a lower incidence of venous thromboembolism.[17] Whether this actually did result in a lower incidence of venous thromboembolism has never been assessed.[17] Society and cultureGeneric namesMestranol is the generic name of the drug and its {{abbrlink|INN|International Nonproprietary Name}}, {{abbrlink|USAN|United States Adopted Name}}, {{abbrlink|USP|United States Pharmacopeia}}, {{abbrlink|BAN|British Approved Name}}, {{abbrlink|DCF|Dénomination Commune Française}}, and {{abbrlink|JAN|Japanese Accepted Name}}, while mestranolo is its {{abbrlink|DCIT|Denominazione Comune Italiana}}.[18][19][20][21]Brand namesMestranol has been marketed under a variety of brand names, mostly or exclusively in combination with progestins, including Devocin, Enavid, Enovid, Femigen, Mestranol, Norbiogest, Ortho-Novin, Ortho-Novum, Ovastol, and Tranel among others.[3][18][22][19] Today, it continues to be sold in combination with progestins under brand names including Lutedion, Necon, Norinyl, Ortho-Novum, and Sophia.[21] AvailabilityMestranol remains available only in the United States, the United Kingdom, Japan, and Chile.[21] It is only marketed in combination with progestins, such as norethisterone.[21] ResearchMestranol has been studied as a male contraceptive and was found to be highly effective.[23][24][25][26] At a dosage of 0.45 mg/day, it suppressed gonadotropin levels, reduced sperm count to zero within 4 to 6 weeks, and decreased libido, erectile function, and testicular size.[23][24][26][25] Gynecomastia occurred in all of the men.[23][24][26][25] These findings contributed to the conclusion that estrogens would be unacceptable as contraceptives for men.[24] References1. ^{{cite journal|last1=Wittlinger|first1=H.|title=Clinical Effects of Estrogens|year=1980|pages=67–71|doi=10.1007/978-3-642-67568-3_10}} {{Estrogens and antiestrogens}}{{Estrogen receptor modulators}}2. ^1 {{cite book|author=Donna Shoupe|title=The Handbook of Contraception: A Guide for Practical Management|url=https://books.google.com/books?id=sczb0Tk_2IwC&pg=PA23|date=7 November 2007|publisher=Springer Science & Business Media|isbn=978-1-59745-150-5|pages=23–|quote=EE is about 1.7 times as potent as the same weight of mestranol.}} 3. ^1 2 {{cite book|author=Lara Marks|title=Sexual Chemistry: A History of the Contraceptive Pill|url=https://books.google.com/books?id=_i-s4biQs7MC&pg=PA75|year=2010|publisher=Yale University Press|isbn=978-0-300-16791-7|pages=75–}} 4. ^1 {{cite book|author=Robert W. Blum|title=Adolescent Health Care: Clinical Issues|url=https://books.google.com/books?id=36PpAgAAQBAJ&pg=PA216|date=22 October 2013|publisher=Elsevier Science|isbn=978-1-4832-7738-7|pages=216–}} 5. ^{{cite book |author1=Faigle, Johann W. |author2=Schenkel, Lotte |editor1=in Fraser |editor2=Ian S. |year=1998 |chapter=Pharmacokinetics of estrogens and progestogens |title=Estrogens and Progestogens in Clinical Practice |pages=273–294 |location=London |publisher=Churchill Livingstone |isbn=0-443-04706-5}} 6. ^{{cite book|author1=Tommaso Falcone|author2=William W. Hurd|title=Clinical Reproductive Medicine and Surgery|url=https://books.google.com/books?id=fOPtaEIKvcIC&pg=PA388|year=2007|publisher=Elsevier Health Sciences|isbn=0-323-03309-1|pages=388–}} 7. ^{{cite book|author=Donna Shoupe|title=The Handbook of Contraception: A Guide for Practical Management|url=https://books.google.com/books?id=sczb0Tk_2IwC&pg=PA23|date=7 November 2007|publisher=Springer Science & Business Media|isbn=978-1-59745-150-5|pages=23–|quote=EE is about 1.7 times as potent as the same weight of mestranol.}} 8. ^{{cite journal | vauthors = Blair RM, Fang H, Branham WS, Hass BS, Dial SL, Moland CL, Tong W, Shi L, Perkins R, Sheehan DM | title = The estrogen receptor relative binding affinities of 188 natural and xenochemicals: structural diversity of ligands | journal = Toxicol. Sci. | volume = 54 | issue = 1 | pages = 138–53 | date = March 2000 | pmid = 10746941 | doi = | url = }} 9. ^{{cite journal|last1=Ruenitz|first1=Peter C.|title=Female Sex Hormones, Contraceptives, And Fertility Drugs|year=2010|doi=10.1002/0471266949.bmc054}} 10. ^{{cite journal | vauthors = Bingel AS, Benoit PS | title = Oral contraceptives: therapeutics versus adverse reactions, with an outlook for the future I | journal = J Pharm Sci | volume = 62 | issue = 2 | pages = 179–200 | date = February 1973 | pmid = 4568621 | doi = 10.1002/jps.2600620202 | url = }} 11. ^{{cite book|author=Gregory Pincus|title=The Control of Fertility|url=https://books.google.com/books?id=ehQlBQAAQBAJ&pg=PA222|date=3 September 2013|publisher=Elsevier|isbn=978-1-4832-7088-3|pages=222–}} 12. ^{{cite book|author=A. Labhart|title=Clinical Endocrinology: Theory and Practice|url=https://books.google.com/books?id=DAgJCAAAQBAJ&pg=PA575|date=6 December 2012|publisher=Springer Science & Business Media|isbn=978-3-642-96158-8|pages=575–}} 13. ^1 2 3 4 5 6 {{cite book|author=Walter Sneader|title=Drug Discovery: A History|url=https://books.google.com/books?id=Cb6BOkj9fK4C&pg=PA202|date=23 June 2005|publisher=John Wiley & Sons|isbn=978-0-471-89979-2|pages=202–}} 14. ^1 2 3 4 5 6 {{cite book|author1=Gretchen M. Lentz|author2=Rogerio A. Lobo|author3=David M. Gershenson |author4=Vern L. Katz |title=Comprehensive Gynecology|url=https://books.google.com/books?id=OmpULog7A_QC&pg=PA224|year=2012|publisher=Elsevier Health Sciences|isbn=0-323-06986-X|pages=224–}} 15. ^{{cite book|author1=Marcus Filshie|author2=John Guillebaud|title=Contraception: Science and Practice|url=https://books.google.com/books?id=Ug3-BAAAQBAJ&pg=PA12|date=22 October 2013|publisher=Elsevier Science|isbn=978-1-4831-6366-6|pages=12–}} 16. ^{{cite journal | vauthors = Billingsley FS | title = Lactation suppression utilizing norethynodrel with mestranol | journal = J Fla Med Assoc | volume = 56 | issue = 2 | pages = 95–7 | year = 1969 | pmid = 4884828 | doi = | url = }} 17. ^1 2 3 {{cite book|author=Jeffrey K. Aronson|title=Meyler's Side Effects of Endocrine and Metabolic Drugs|url=https://books.google.com/books?id=BWMeSwVwfTkC&pg=PA224|date=21 February 2009|publisher=Elsevier|isbn=978-0-08-093292-7|pages=224–}} 18. ^1 2 3 {{cite book|author=J. Elks|title=The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies|url=https://books.google.com/books?id=0vXTBwAAQBAJ&pg=PA775|date=14 November 2014|publisher=Springer|isbn=978-1-4757-2085-3|pages=775–}} 19. ^1 2 3 {{cite book|title=Index Nominum 2000: International Drug Directory|url=https://books.google.com/books?id=5GpcTQD_L2oC&pg=PA656|year=2000|publisher=Taylor & Francis|isbn=978-3-88763-075-1|pages=656–}} 20. ^1 2 3 4 {{cite book|author1=I.K. Morton|author2=Judith M. Hall|title=Concise Dictionary of Pharmacological Agents: Properties and Synonyms|url=https://books.google.com/books?id=tsjrCAAAQBAJ&pg=PA177|date=6 December 2012|publisher=Springer Science & Business Media|isbn=978-94-011-4439-1|pages=177–}} 21. ^1 2 3 4 5 6 7 8 https://www.drugs.com/international/mestranol.html 22. ^{{cite book|author=William Andrew Publishing|title=Pharmaceutical Manufacturing Encyclopedia, 3rd Edition|url=https://books.google.com/books?id=_J2ti4EkYpkC&pg=PA2109-IA88|date=22 October 2013|publisher=Elsevier|isbn=978-0-8155-1856-3|pages=2109–}} 23. ^1 2 {{cite journal | vauthors = Dorfman RI | title = Pharmacology of estrogens-general | journal = Pharmacol. Ther. | volume = 9 | issue = 1 | pages = 107–19 | date = 1980 | pmid = 6771777 | doi = 10.1016/0163-7258(80)90018-2 | url = }} 24. ^1 2 3 {{cite journal | vauthors = Jackson H | title = Progress towards a male oral contraceptive | journal = Clin Endocrinol Metab | volume = 4 | issue = 3 | pages = 643–63 | date = November 1975 | pmid = 776453 | doi = 10.1016/S0300-595X(75)80051-X | url = }} 25. ^1 2 {{cite book|last1=Oettel|first1=M|chapter=Estrogens and Antiestrogens in the Male|pages=505–571|doi=10.1007/978-3-642-60107-1_25|editor1=Michael Oettel|editor2=Ekkehard Schillinger|title=Estrogens and Antiestrogens II: Pharmacology and Clinical Application of Estrogens and Antiestrogen|url=https://books.google.com/books?id=wBvyCAAAQBAJ&pg=PA538|date=1999|publisher=Springer Science & Business Media|isbn=978-3-642-60107-1|issn=0171-2004}} 26. ^1 2 {{cite journal | vauthors = Heller CG, Moore DJ, Paulsen CA, Nelson WO, Laidlaw WM | title = Effects of progesterone and synthetic progestins on the reproductive physiology of normal men | journal = Fed. Proc. | volume = 18 | issue = | pages = 1057–65 | date = December 1959 | pmid = 14400846 | doi = | url = https://www.popline.org/node/472874}} 7 : Alkynes|Diols|Estranes|Estrogen ethers|Hormonal contraception|Prodrugs|Synthetic estrogens |
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