Cyclofenilのソースを表示

{{Short description|Chemical compound}}
{{Distinguish|Cycloguanil}}
{{Drugbox
| IUPAC_name = [4-[(4-Acetoxyphenyl)-cyclohexylidene-methyl]phenyl] acetate
| image = Cyclofenil.svg
| image_class = skin-invert-image
| width = 250px

<!--Clinical data-->
| tradename = Sexovid, others
| Drugs.com = {{drugs.com|international|cyclofenil}}
| pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X -->
| pregnancy_US = <!-- A / B / C / D / X -->
| pregnancy_category =
| legal_AU = <!-- S2, S3, S4, S5, S6, S7, S8, S9 or Unscheduled-->
| legal_CA = <!-- Schedule I, II, III, IV, V, VI, VII, VIII -->
| legal_UK = <!-- GSL, P, POM, CD, or Class A, B, C -->
| legal_US = <!-- OTC / Rx-only / Schedule I, II, III, IV, V -->
| legal_status =
| routes_of_administration = [[Oral administration|By mouth]]
| class = [[Selective estrogen receptor modulator]]; [[Progonadotropin]]

<!--Pharmacokinetic data-->
| bioavailability =
| protein_bound =
| metabolism =
| elimination_half-life = 18–29 hours<ref name="InslerLunenfeld1993" /><ref name="BlanksteinMashiach1986" />
| excretion =

<!--Identifiers-->
| CAS_number = 2624-43-3
| ATC_prefix = G03
| ATC_suffix = GB01
| PubChem = 2898
| DrugBank =
| ChEMBL = 141305
| ChemSpiderID = 2795
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = J468V64WZ1
| KEGG = D01281
| synonyms = Cyclophenil; F-6066; H-3452; ICI-48213; bis(''p''-Acetoxyphenyl)-cyclohexylidenemethane

<!--Chemical data-->
| C=23 | H=24 | O=4
| SMILES = O=C(Oc3ccc(C(/c1ccc(OC(=O)C)cc1)=C2\CCCCC2)cc3)C
}}
<!-- Definition and medical uses -->
'''Cyclofenil''', sold under the brand name '''Sexovid''' among others, is a [[selective estrogen receptor modulator]] (SERM) medication which is used as a [[progonadotropin|gonadotropin stimulant]] or [[ovulation inducer]] and in [[menopausal hormone therapy]] in women.<ref name="Martindale" /><ref name="Elks2014">{{cite book| vauthors = Elks J |title=The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies|url=https://books.google.com/books?id=0vXTBwAAQBAJ&pg=PA329|date=14 November 2014|publisher=Springer|isbn=978-1-4757-2085-3|pages=329–}}</ref><ref name="IndexNominum2000">{{cite book|title=Index Nominum 2000: International Drug Directory|url=https://books.google.com/books?id=5GpcTQD_L2oC&pg=PA284|date=January 2000|publisher=Taylor & Francis|isbn=978-3-88763-075-1|pages=284–}}</ref><ref name="Drugs.com">{{Cite web |url= https://www.drugs.com/international/cyclofenil.html |title=List of 7 Menopausal Disorders Medications Compared | work = Drugs.com }}</ref> It is mostly no longer available.<ref name="Drugs.com" /> The medication is taken [[oral administration|by mouth]].<ref name="Seyffart2012">{{cite book| vauthors = Seyffart G | chapter = Cyclofenil |title=Drug Dosage in Renal Insufficiency| chapter-url=https://books.google.com/books?id=OavnCAAAQBAJ&pg=PA166|date=6 December 2012|publisher=Springer Science & Business Media|isbn=978-94-011-3804-8|pages=166–}}</ref><ref name="MozayaniRaymon2003" /><ref name="MeniruBrinsden1997">{{cite book| vauthors = Meniru GI, Craft IL | chapter = Ovarian stimulation for assisted reproduction technologies| veditors = Meniru GI, Brinsden PR, Craft IL |title=A Handbook of Intrauterine Insemination| chapter-url = https://books.google.com/books?id=UpNScYN8B2YC&pg=PA58 |date=31 July 1997 |publisher=Cambridge University Press |isbn=978-0-521-58676-4 |pages=58–59,207 }}</ref>

<!-- Side effects and mechanism -->
[[Side effect]]s of cyclofenil include [[liver toxicity]] among others.<ref name="CameronFeuer2012" /> It is a [[selective estrogen receptor modulator]] (SERM) and hence is a mixed [[agonist]]–[[receptor antagonist|antagonist]] of the [[estrogen receptor]] (ER), the [[biological target]] of [[estrogen]]s like [[estradiol]].<ref name="MozayaniRaymon2003" /> It has [[antiestrogen]]ic effects on the [[hypothalamic–pituitary–gonadal axis]] and hence can increase [[sex hormone]] production and stimulate [[ovulation]].<ref name="MozayaniRaymon2003" /><ref name="ZuckermanWeir2013" />

<!-- History, society, and culture -->
Cyclofenil was introduced for medical use in 1970.<ref name="Publishing2013" /> It has been mostly discontinued, but remains available in a few countries, including [[Brazil]], [[Italy]], and [[Japan]].<ref name="Drugs.com" /><ref name="Micromedex" /><ref name="Martindale" /> It has been used as a [[doping agent]] by male [[athlete]]s.<ref name="MozayaniRaymon2003" />

==Medical use==
Cyclofenil is used to treat [[menstrual disturbance]]s and [[anovulation|anovulatory]] [[infertility]] caused by insufficiency of the [[hypothalamic–pituitary–gonadal axis]] in women.<ref name="Martindale" /> It has also been used to treat [[menopausal symptoms]].<ref name="Martindale" /> The medication is generally used at a dosage of 400 to 600&nbsp;mg per day.<ref name="Martindale" /><ref name="MozayaniRaymon2003" /><ref name="MeniruBrinsden1997" />

===Available forms===
Cyclofenil has been available in the form of 100, 200, and 400&nbsp;mg [[oral administration|oral]] [[tablet (pharmacy)|tablet]]s.<ref name="MozayaniRaymon2003">{{cite book | vauthors = von Deutsch DA, Abukhalaf IK, Socci RR | chapter = Anabolic Doping Agents | veditors = Mozayani A, Raymon L |title=Handbook of Drug Interactions: A Clinical and Forensic Guide | chapter-url = https://books.google.com/books?id=dwMyBwAAQBAJ&pg=PA555 |date=15 October 2003|publisher=Springer Science & Business Media|isbn=978-1-59259-654-6|pages=555–}}</ref>

==Non-medical use==
Cyclofenil has been used by male [[athlete]]s to increase [[testosterone]] levels.<ref name="MozayaniRaymon2003" /> It is not effective for this purpose in women.<ref name="MozayaniRaymon2003" />

==Contraindications==
Cyclofenil is [[contraindication|contraindicated]] during [[pregnancy]] and in those with severe [[liver disease]] and unexplained [[uterine bleeding]].<ref name="MutschlerDerendorf1995">{{cite book| vauthors = Mutschler E, Derendorf H, Schäfer-Korting M, Elrod K, Estes KS | chapter = Ovaries |title=Drug Actions: Basic Principles and Therapeutic Aspects| chapter-url = https://books.google.com/books?id=IvN4mZxraMkC&pg=PA294|year=1995|publisher=CRC Press|isbn=978-0-8493-7774-7|pages=294–}}</ref>

==Side effects==
Cyclofenil is associated with a relatively high incidence of [[hepatotoxicity]].<ref name="CameronFeuer2012">{{cite book| vauthors = Zimmerman HJ, Ishak KG | chapter = Steroids and Other Hormones| veditors = Cameron R, Feuer G, de la Iglesia F |title=Drug-Induced Hepatotoxicity| chapter-url = https://books.google.com/books?id=xZf-CAAAQBAJ&pg=PA565|date=6 December 2012|publisher=Springer Science & Business Media|isbn=978-3-642-61013-4|pages=565–}}</ref> Biochemical signs of undesirable liver changes have been observed in 35% or more of individuals and 1% of individuals experience overt [[hepatitis]].<ref name="CameronFeuer2012" />

==Pharmacology==

===Pharmacodynamics===
Cyclofenil is a SERM, or a mixed [[agonist]] and [[receptor antagonist|antagonist]] of the [[estrogen receptor]]s (ERs).<ref name="MozayaniRaymon2003" /> It is described as a relatively weak/mild SERM.<ref name="MozayaniRaymon2003" /> The medication is generally less effective than other SERMs.<ref name="Tatford2012" /> The medication is an "impeded estrogen" and is thought to work as a [[progonadotropin]] by blocking the actions of estrogens in the [[pituitary gland]] and [[hypothalamus]], thereby disinhibiting release of the [[gonadotropin]]s [[luteinizing hormone]] and [[follicle-stimulating hormone]].<ref name="ZuckermanWeir2013" /> In men, cyclofenil can increase [[testosterone]] levels due its progonadotropic effects.<ref name="MozayaniRaymon2003" />

===Pharmacokinetics===
In terms of [[distribution (pharmacokinetics)|distribution]], cyclofenil acts both [[central nervous system|centrally]] and peripherally.<ref name="Tatford2012">{{cite book| vauthors = Tatford EP | chapter = Excessive Vaginal Bleeding |title=Problems in Gynaecology| chapter-url = https://books.google.com/books?id=q0inBgAAQBAJ&pg=PA105|date=6 December 2012|publisher=Springer Science & Business Media|isbn=978-94-009-4125-0|pages=105–106}}</ref> The [[elimination half-life]] of cyclofenil after a single 200&nbsp;mg dose is 18 to 29&nbsp;hours.<ref name="InslerLunenfeld1993">{{cite book | vauthors = Insler V, Lunenfeld B |title=Infertility: Male and Female|url=https://books.google.com/books?id=KCNsAAAAMAAJ|date=January 1993|publisher=Churchill Livingstone|isbn=978-0-443-04514-1|page=458}}</ref><ref name="BlanksteinMashiach1986">{{cite book| vauthors = Blankstein J, Mashiach S, Lunenfeld B |title=Ovulation Induction and in Vitro Fertilization|url=https://books.google.com/books?id=aYVsAAAAMAAJ|date=1 July 1986|publisher=Year Book Medical Publishers|isbn=978-0-8151-0871-9|page=113}}</ref>

==Chemistry==
Cyclofenil is a [[nonsteroidal]] SERM and is closely related structurally to [[triphenylethylene]] SERMs like [[clomifene]] and [[tamoxifen]].<ref name="MeniruBrinsden1997" /> It has been referred to as a diphenylethylene [[chemical derivative|derivative]], differing from triphenylethylenes only by the replacement of one of the [[phenyl ring]]s with a [[cyclohexane]] ring.<ref name="HorskyPresl2012">{{cite book| vauthors = Horsky J | chapter = Oestrogens | veditors = Horsky J, Presl J |title=Ovarian Function and its Disorders: Diagnosis and Therapy|chapter-url=https://books.google.com/books?id=7IrpCAAAQBAJ&pg=PA92|date=6 December 2012|publisher=Springer Science & Business Media|isbn=978-94-009-8195-9|pages=92–}}</ref><ref name="ZuckermanWeir2013">{{cite book | vauthors = Bishop PM | chapter = Clinical Manifestations of Disorders of the Human Ovary| veditors = Zuckerman S, Weir BJ |title=Physiology| chapter-url = https://books.google.com/books?id=4R_FAgAAQBAJ&pg=PA209|date=22 October 2013|publisher=Elsevier Science|isbn=978-1-4832-5975-8|pages=209–}}</ref>

==History==
Cyclofenil was first introduced for medical use in 1970 under the brand name Ondogyne in [[France]].<ref name="Publishing2013">{{cite book|author=William Andrew Publishing|title=Pharmaceutical Manufacturing Encyclopedia | edition = 3rd |url=https://books.google.com/books?id=_J2ti4EkYpkC&pg=PA1162|date=22 October 2013|publisher=Elsevier|isbn=978-0-8155-1856-3|pages=1162–}}</ref> Subsequently, it was introduced throughout the world under a variety of other brand names, including its most well-known brand name Sexovid.<ref name="Publishing2013" />

==Society and culture==

===Generic names===
''Cyclofenil'' is the [[English language|English]] [[generic term|generic name]] of the drug and its {{abbrlink|INN|International Nonproprietary Name}}, {{abbrlink|USAN|United States Adopted Name}}, and {{abbrlink|BAN|British Approved Name}}.<ref name="Elks2014" /><ref name="IndexNominum2000" /><ref name="Drugs.com" />

===Brand names===
Cyclofenil has been marketed under a variety of brand names including Ciclifen, Fertodur, Gyneuro, Klofenil, Menoferil, Menopax, Neoclym, Oginex, Ondonid, Ondogyne, Rehibin, Sexadieno, Sexovar, and Sexovid.<ref name="NegwerScharnow2001">{{cite book| vauthors = Negwer M, Scharnow HG |title=Organic-chemical drugs and their synonyms: (an international survey)|url=https://books.google.com/books?id=zmpqAAAAMAAJ|year=2001|publisher=Wiley-VCH|isbn=978-3-527-30247-5|page=2397}}</ref><ref name="Publishing2013" /><ref name="Micromedex">{{cite web | title=IBM Watson Health Products | website=IBM Watson Health Products | url=http://www.micromedexsolutions.com/ | access-date=2021-11-01}}</ref>

===Availability===
Cyclofenil remains available today only in [[Brazil]], [[Italy]], and [[Japan]].<ref name="Drugs.com" /><ref name="Micromedex" /><ref name="Martindale" /> In the past, it has also been available in [[France]], [[Germany]], [[Mexico]], [[Sweden]], [[Switzerland]], [[Turkey]], and the [[United Kingdom]].<ref name="IndexNominum2000" /><ref name="Publishing2013" /><ref name="Micromedex" /><ref name="Martindale">{{cite book | veditors = Sweetman SC |chapter=Sex hormones and their modulators |title=Martindale: The Complete Drug Reference |edition=36th |year=2009 |publisher=Pharmaceutical Press |location=London|isbn=978-0-85369-840-1|page=2088}}</ref>

===Regulation===
Cyclofenil is included on the [[World Anti-Doping Agency]] list of illegal doping agents in sport.<ref name="MottramChester2014">{{cite book| vauthors = Chester N | chapter = Hormone and metabolic modulators | veditors = Mottram DR, Chester N |title=Drugs in Sport| chapter-url = https://books.google.com/books?id=ESFWBQAAQBAJ&pg=PA117|date=13 November 2014|publisher=Routledge|isbn=978-1-134-70800-0|pages=117–}}</ref><ref name="Team2004">{{cite book|author=Ed The Emtree Editorial Team|title=Doping Search Guide 2004: Over 10,000 Substance Names in Reference to the 2004 WADA (World Anti-Doping Agency) List of Prohibited Substances and Methods|url=https://books.google.com/books?id=Y9ULAQAAMAAJ|date=1 January 2004|publisher=Elsevier|isbn=978-0-444-51752-4|page=82}}</ref>

==Research==
Cyclofenil was investigated as a possible treatment for [[scleroderma]] in the 1980s, but was found to be ineffective.<ref name="pmid2406809">{{cite journal |vauthors=Torres MA, Furst DE |title=Treatment of generalized systemic sclerosis |journal=Rheum Dis Clin North Am |volume=16 |issue=1 |pages=217–41 |date=February 1990 |doi=10.1016/S0889-857X(21)01050-4 |pmid=2406809}}</ref> Later study of its efficacy in treating [[Raynaud's phenomenon]] in people with scleroderma also found no significant benefit.<ref name="pmid10796397">{{cite journal |vauthors=Pope J, Fenlon D, Thompson A | veditors = Pope J |title=Cyclofenil for Raynaud's phenomenon in progressive systemic sclerosis |journal=[[Cochrane collaboration|Cochrane Database Syst Rev]] |issue=2 |pages=CD000955 |year=2000 |volume=1998 |pmid=10796397 |doi=10.1002/14651858.CD000955|display-authors=etal|pmc=7032887 }}</ref>

==References==
{{Reflist}}

{{Estrogens and antiestrogens}}
{{Estrogen receptor modulators}}

[[Category:Acetate esters]]
[[Category:Hepatotoxins]]
[[Category:Progonadotropins]]
[[Category:Selective estrogen receptor modulators]]
[[Category:Bis(4-hydroxyphenyl)methanes]]