Wikipedia:WikiProject Chemicals/Chembox validation/VerifiedDataSandbox and Mitotane: Difference between pages

{{Short description|Chemical compound}}

{{Use dmy dates|date=June 2024}}

{{cs1 config |name-list-style=vanc |display-authors=6}}

| verifiedrevid =

| width =

| image2 = Mitotane-(2S)-enantiomer-from-xtal-3D-bs-17.png

| chirality = [[Racemic mixture]]

| tradename =

| =

| pregnancy_category =

| routes_of_administration = Oral

| ATC_prefix = L01

| ATC_suffix = XX23

| ATC_supplemental =

| legal_CA = Rx-only

| legal_CA_comment = <ref>{{cite web | title=Product monograph brand safety updates | website=[[Health Canada]] | date=7 July 2016 | url=https://www.canada.ca/en/health-canada/services/drugs-health-products/drug-products/drug-product-database/label-safety-assessment-update/product-monograph-brand-safety-updates.html | access-date=3 April 2024}}</ref>

| legal_EU = Rx-only

| legal_EU_comment = <ref>{{cite web | title=Lysodren EPAR | website=European Medicines Agency | date=12 June 2002 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/lysodren | access-date=27 June 2024}}</ref>

| metabolism =

| metabolites =

| elimination_half-life = days

| excretion =

| IUPHAR_ligand = 6957

| = {{cascite|correct|}}

| synonyms = 1,1-(Dichlorodiphenyl)-2,2-dichloroethane; o,p'-DDD

| C=14 | H=10 | Cl=4

| = Clc1ccccc1C(c2ccc(Cl)cc2)C(Cl)Cl

<!--Physical data-->

| melting_point = 76

| melting_high = 78

'''Mitotane''', sold under the brand name '''Lysodren''', is a [[steroidogenesis inhibitor]] and [[cytostatic]] [[antineoplastic]] medication which is used in the treatment of [[adrenocortical carcinoma]] and [[Cushing's syndrome]].<ref name="JamesonGroot2010">{{cite book| vauthors = Cavagnini F, Giraldi FP | chapter = Adrenal Causes of Hypercortisolism | veditors = Jameson JL, De Groot LJ |title=Endocrinology - E-Book: Adult and Pediatric| chapter-url= https://books.google.com/books?id=W4dZ-URK8ZoC&pg=PA1888|date=18 May 2010|publisher=Elsevier Health Sciences|isbn=978-1-4557-1126-0|pages=1888–}}</ref><ref name="pmid15898346">{{cite journal | vauthors = Hahner S, Fassnacht M | title = Mitotane for adrenocortical carcinoma treatment | journal = Current Opinion in Investigational Drugs | volume = 6 | issue = 4 | pages = 386–394 | date = April 2005 | pmid = 15898346 }}</ref><ref name="Bronstein2010">{{cite book| vauthors = Dang C, Trainer PJ | chapter = Medical Management of Cushing's Syndrome| veditors = Bronstein MD |title=Cushing's Syndrome: Pathophysiology, Diagnosis and Treatment| chapter-url=https://books.google.com/books?id=5_ulQAM9OZYC&pg=PA156|date=1 October 2010|publisher=Springer Science & Business Media|isbn=978-1-60327-449-4|pages=156–}}</ref><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=PA382|date=14 November 2014|publisher=Springer|isbn=978-1-4757-2085-3|pages=382–}}</ref> It is a [[chemical derivative|derivative]] of the early [[insecticide]] [[DDT]] and an [[isomer]] of {{abbrlink|p,p'-DDD|dichlorodiphenyldichloroethane}} (4,4'-dichlorodiphenyldichloroethane) and is also known as '''2,4'-(dichlorodiphenyl)-2,2-dichloroethane''' ('''o,p'-DDD''').<ref name="PubChem">{{cite web | title = Mitotane | url = https://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=4211 | work = PubChem | publisher = U.S. National Library of Medicine }}</ref>

==Medical uses==

Mitotane has been produced by [[Bristol Myers Squibb]] but it is marketed as an [[orphan drug]] for adrenocortical carcinoma due to the small number of patients in need of it. Its main use is in those patients who have persistent disease despite surgical resection, those who are not surgical candidates, or those who have metastatic disease. In a 2007 retrospective study of 177 patients from 1985 to 2005 showed a significant increase in the recurrence-free interval after radical surgery followed by mitotane when compared to surgery alone.<ref name=":0">{{cite journal | vauthors = Terzolo M, Angeli A, Fassnacht M, Daffara F, Tauchmanova L, Conton PA, Rossetto R, Buci L, Sperone P, Grossrubatscher E, Reimondo G, Bollito E, Papotti M, Saeger W, Hahner S, Koschker AC, Arvat E, Ambrosi B, Loli P, Lombardi G, Mannelli M, Bruzzi P, Mantero F, Allolio B, Dogliotti L, Berruti A | display-authors = 6 | title = Adjuvant mitotane treatment for adrenocortical carcinoma | journal = The New England Journal of Medicine | volume = 356 | issue = 23 | pages = 2372–2380 | date = June 2007 | pmid = 17554118 | doi = 10.1056/NEJMoa063360 | hdl-access = free | hdl = 2318/37317 }}</ref> The drug is also sometimes used in the treatment of [[Cushing's syndrome]].<ref name="Bronstein2010" />

==Side effects==

The use of mitotane is unfortunately limited by [[side effect]]s,<ref name="HarrisBouloux2014" /> which, as reported by Schteingart et al., include [[anorexia (symptom)|anorexia]] and [[nausea]] (88%), [[diarrhea]] (38%), [[vomiting]] (23%), decreased [[memory]] and ability to concentrate (50%), [[rash]] (23%), [[gynecomastia]] (50%), [[arthralgia]] (19%), and [[leukopenia]] (7%).<ref>{{cite journal | vauthors = Schteingart DE, Motazedi A, Noonan RA, Thompson NW | title = Treatment of adrenal carcinomas | journal = Archives of Surgery | volume = 117 | issue = 9 | pages = 1142–1146 | date = September 1982 | pmid = 7115060 | doi = 10.1001/archsurg.1982.01380330010004 }}</ref>

==Pharmacology==

===Pharmacodynamics===

Mitotane is an inhibitor of the [[adrenal cortex]]. It acts as an [[enzyme inhibitor|inhibitor]] of [[cholesterol side-chain cleavage enzyme]] (P450scc, CYP11A1), and also of [[11β-hydroxylase]] (CYP11B1), [[18-hydroxylase]] (aldosterone synthase, CYP11B2), and [[3β-hydroxysteroid dehydrogenase]] (3β-HSD) to a lesser extent.<ref name="JamesonGroot2010" /><ref name="HarrisBouloux2014">{{cite book| vauthors = Tzanela M, Vassiliadi DA, Tsagarakis S | chapter = Coincidental adrenal masses and adrenal cancer| veditors = Harris PE, Bouloux PM |title=Endocrinology in Clinical Practice | edition = Second | chapter-url= https://books.google.com/books?id=tZE-AwAAQBAJ&pg=PA216 |date=24 March 2014|publisher=CRC Press|isbn=978-1-84184-951-5|pages=216–}}</ref> In addition, mitotane has direct and selective [[cytotoxic]] effects on the adrenal cortex, via an unknown mechanism, and thereby induces permanent [[Adrenal insufficiency|adrenal atrophy]] similarly to DDD.<ref name="MPHMD2011">{{cite book| vauthors = Sojka WS, Raizer J| chapter = Neurologic Complications of Hormonal Chemotherapies | veditors = Lee EQ, Schiff D, Wen PY |title=Neurologic Complications of Cancer Therapy| chapter-url=https://books.google.com/books?id=52qyu5XPqM4C&pg=PA179 |date=28 September 2011|publisher=Demos Medical Publishing|isbn=978-1-61705-019-0|pages=179–}}</ref><ref name="Kannan2012">{{cite book | vauthors = Kannan CR | chapter = Cushing's Syndrome |title=The Adrenal Gland| chapter-url= https://books.google.com/books?id=WqXSBwAAQBAJ&pg=PA160|date=6 December 2012|publisher=Springer Science & Business Media|isbn=978-1-4613-1001-3|pages=160–}}</ref>

==Chemistry==

[[Structural analog|Analogue]]s of mitotane include [[aminoglutethimide]], [[amphenone B]], and [[metyrapone]].

==History==

Mitotane was introduced in 1960 for the treatment of [[adrenocortical carcinoma]].<ref name="Bronstein2010" />

==Society and culture==

===Generic names===

Mitotane is the [[generic term|generic name]] of the medication and its {{abbrlink|INN|International Nonproprietary Name}}, {{abbrlink|USAN|United States Adopted Name}}, {{abbrlink|BAN|British Approved Name}}, and {{abbrlink|JAN|Japanese Accepted Name}}.<ref name="Elks2014" /><ref name="IndexNominum2000">{{cite book|title=Index Nominum 2000: International Drug Directory|url=https://books.google.com/books?id=5GpcTQD_L2oC&pg=PA697|year=2000|publisher=Taylor & Francis|isbn=978-3-88763-075-1|pages=697–}}</ref>

===Brand names===

Mitotane is sold under the brand name Lysodren.<ref name="Elks2014" />

==Veterinary use==

Mitotane is also used to treat [[Cushing's disease]] ([[pituitary]]-dependent [[Cushing's syndrome]]) in [[dog]]s. The medication is used in the controlled destruction of adrenal tissue, leading to a decrease in cortisol production.<ref>{{cite web|archive-date=21 October 2007|archive-url=https://web.archive.org/web/20071021093745/http://www.michvma.org/documents/MVC%20Proceedings/Nichols2.pdf|title=Canine Cushing's Syndrome: Diagnosis and Treatment Part 1: Typical, Atypical, and Pseudo-Cushing's Disease|url=http://www.michvma.org/documents/MVC%20Proceedings/Nichols2.pdf|vauthors=Nichols R}}</ref>

== References ==

{{Reflist}}

== Further reading ==

{{refbegin}}

* {{cite journal | vauthors = Komissarenko VP, Chelnakova IS, Mikosha AS | title = Effect of o,p-dichlorodiphenyldichloroethane and perthane in vitro on glutathione reductase activity in the adrenals of dogs and guinea pigs | doi = 10.1007/BF00800110 | year = 1978 | journal = Bulletin of Experimental Biology and Medicine | volume = 85 | issue = 2 | pages = 152–154| s2cid = 23181221 }}

{{refend}}

== External links ==

* {{cite web | publisher = Government of Canada | title = Mitotane – information sheet | url = http://www.chemicalsubstanceschimiques.gc.ca/challenge-defi/summary-sommaire/batch-lot-12/53-19-0-eng.php | date = 16 October 2017 }}

* {{cite web | publisher = Environment Canada & Health Canada | url = http://www.ec.gc.ca/ese-ees/434E69F1-1490-4CD3-A0BB-4A15CA8D0313/RM%20Scope_B12%20-%2053-19-0_EN.pdf | archive-url = https://web.archive.org/web/20140810215750/http://www.ec.gc.ca/ese-ees/434E69F1-1490-4CD3-A0BB-4A15CA8D0313/RM%20Scope_B12%20-%2053-19-0_EN.pdf | archive-date = 10 August 2014 | title = RISK MANAGEMENT SCOPE for Benzene, 1-chloro-2-[2,2-dichloro-1-(4-chlorophenyl)ethyl&#93;- (Mitotane)] | date = July 2013 }}

{{Chemotherapeutic agents}}

{{Glucocorticoids and antiglucocorticoids}}

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[[Category:3β-Hydroxysteroid dehydrogenase inhibitors]]

[[Category:11β-Hydroxylase inhibitors]]

[[Category:Aldosterone synthase inhibitors]]

[[Category:Antiglucocorticoids]]

[[Category:Antineoplastic drugs]]

[[Category:Chloroarenes]]

[[Category:Cholesterol side-chain cleavage enzyme inhibitors]]

[[Category:CYP3A4 inducers]]

[[Category:Organochlorides]]

[[Category:Orphan drugs]]

[[Category:Steroidogenesis inhibitors]]