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Wikipedia

Mitotane

January 01, 1970

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.[3][4][5][6] It is a derivative of the early insecticide DDT and an isomer of p,p'-DDDTooltip dichlorodiphenyldichloroethane (4,4'-dichlorodiphenyldichloroethane) and is also known as 2,4'-(dichlorodiphenyl)-2,2-dichloroethane (o,p'-DDD).[7]

Mitotane
Clinical data
Trade namesLysodren
Other names1,1-(Dichlorodiphenyl)-2,2-dichloroethane; o,p'-DDD
AHFS/Drugs.comMonograph
MedlinePlusa608050
License data
Routes of
administration		By mouth
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability40%
Protein binding6%
Elimination half-life18–159 days
Identifiers
  • (RS)-1-chloro-2-[2,2-dichloro-1-(4-chlorophenyl)-ethyl]-benzene
CAS Number
  • 53-19-0 Y
PubChem CID
  • 4211
IUPHAR/BPS
  • 6957
DrugBank
  • DB00648 Y
ChemSpider
  • 4066 Y
UNII
  • 78E4J5IB5J
KEGG
  • D00420 Y
ChEMBL
  • ChEMBL1670 Y
CompTox Dashboard (EPA)
  • DTXSID9020372
ECHA InfoCard100.000.152
Chemical and physical data
FormulaC14H10Cl4
Molar mass320.03 g·mol−1
3D model (JSmol)
  • Interactive image
ChiralityRacemic mixture
Melting point76 to 78 °C (169 to 172 °F)
  • Clc1ccccc1C(c2ccc(Cl)cc2)C(Cl)Cl
  • InChI=1S/C14H10Cl4/c15-10-7-5-9(6-8-10)13(14(17)18)11-3-1-2-4-12(11)16/h1-8,13-14H Y
  • Key:JWBOIMRXGHLCPP-UHFFFAOYSA-N Y
  (verify)

Medical uses edit

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.[8] The drug is also sometimes used in the treatment of Cushing's syndrome.[5]

Side effects edit

The use of mitotane is unfortunately limited by side effects,[9] which, as reported by Schteinberg et al., include anorexia and nausea (88%), diarrhea (38%), vomiting (23%), decreased memory and ability to concentrate (50%), rash (23%), gynecomastia (50%), arthralgia (19%), and leukopenia (7%).[10]

Pharmacology edit

Pharmacodynamics edit

Mitotane is an inhibitor of the adrenal cortex. It acts as an 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.[3][9] In addition, mitotane has direct and selective cytotoxic effects on the adrenal cortex, via an unknown mechanism, and thereby induces permanent adrenal atrophy similarly to DDD.[11][12]

Chemistry edit

Analogues of mitotane include aminoglutethimide, amphenone B, and metyrapone.

History edit

Mitotane was introduced in 1960 for the treatment of adrenocortical carcinoma.[5]

Society and culture edit

Generic names edit

Mitotane is the generic name of the medication and its INNTooltip International Nonproprietary Name, USANTooltip United States Adopted Name, BANTooltip British Approved Name, and JANTooltip Japanese Accepted Name.[6][13]

Brand names edit

Mitotane is sold under the brand name Lysodren.[6]

Veterinary use edit

Mitotane is also used to treat Cushing's disease (pituitary-dependent Cushing's syndrome) in dogs. The medication is used in the controlled destruction of adrenal tissue, leading to a decrease in cortisol production.[14]

References edit

  1. ^ "FDA-sourced list of all drugs with black box warnings (Use Download Full Results and View Query links.)". nctr-crs.fda.gov. FDA. Retrieved 22 Oct 2023.
  2. ^ "Product monograph brand safety updates". Health Canada. 7 July 2016. Retrieved 3 April 2024.
  3. ^ a b Cavagnini F, Giraldi FP (18 May 2010). "Adrenal Causes of Hypercortisolism". In Jameson JL, De Groot LJ (eds.). Endocrinology - E-Book: Adult and Pediatric. Elsevier Health Sciences. pp. 1888–. ISBN 978-1-4557-1126-0.
  4. ^ Hahner S, Fassnacht M (April 2005). "Mitotane for adrenocortical carcinoma treatment". Current Opinion in Investigational Drugs. 6 (4): 386–394. PMID 15898346.
  5. ^ a b c Dang C, Trainer PJ (1 October 2010). "Medical Management of Cushing's Syndrome". In Bronstein MD (ed.). Cushing's Syndrome: Pathophysiology, Diagnosis and Treatment. Springer Science & Business Media. pp. 156–. ISBN 978-1-60327-449-4.
  6. ^ a b c Elks J (14 November 2014). The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. Springer. pp. 382–. ISBN 978-1-4757-2085-3.
  7. ^ "Mitotane". PubChem. U.S. National Library of Medicine.
  8. ^ Terzolo M, Angeli A, Fassnacht M, Daffara F, Tauchmanova L, Conton PA, et al. (June 2007). "Adjuvant mitotane treatment for adrenocortical carcinoma". The New England Journal of Medicine. 356 (23): 2372–2380. doi:10.1056/NEJMoa063360. hdl:2318/37317. PMID 17554118.
  9. ^ a b Tzanela M, Vassiliadi DA, Tsagarakis S (24 March 2014). "Coincidental adrenal masses and adrenal cancer". In Harris PE, Bouloux PM (eds.). Endocrinology in Clinical Practice (Second ed.). CRC Press. pp. 216–. ISBN 978-1-84184-951-5.
  10. ^ Schteingart DE, Motazedi A, Noonan RA, Thompson NW (September 1982). "Treatment of adrenal carcinomas". Archives of Surgery. 117 (9): 1142–1146. doi:10.1001/archsurg.1982.01380330010004. PMID 7115060.
  11. ^ Sojka WS, Raizer J (28 September 2011). "Neurologic Complications of Hormonal Chemotherapies". In Lee EQ, Schiff D, Wen PY (eds.). Neurologic Complications of Cancer Therapy. Demos Medical Publishing. pp. 179–. ISBN 978-1-61705-019-0.
  12. ^ Kannan CR (6 December 2012). "Cushing's Syndrome". The Adrenal Gland. Springer Science & Business Media. pp. 160–. ISBN 978-1-4613-1001-3.
  13. ^ Index Nominum 2000: International Drug Directory. Taylor & Francis. 2000. pp. 697–. ISBN 978-3-88763-075-1.
  14. ^ Nichols R. (PDF). Archived from the original (PDF) on 2007-10-21.

Further reading edit

  • Komissarenko VP, Chelnakova IS, Mikosha AS (1978). "Effect of o,p-dichlorodiphenyldichloroethane and perthane in vitro on glutathione reductase activity in the adrenals of dogs and guinea pigs". Bulletin of Experimental Biology and Medicine. 85 (2): 152–154. doi:10.1007/BF00800110. S2CID 23181221.

External links edit

  • "Mitotane – information sheet". Government of Canada. 2017-10-16.
  • (PDF). Environment Canada & Health Canada. July 2013. Archived from the original (PDF) on 10 August 2014.

January 01, 1970
mitotane, sold, under, brand, name, lysodren, steroidogenesis, inhibitor, cytostatic, antineoplastic, medication, which, used, treatment, adrenocortical, carcinoma, cushing, syndrome, derivative, early, insecticide, isomer, dddtooltip, dichlorodiphenyldichloro. 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 3 4 5 6 It is a derivative of the early insecticide DDT and an isomer of p p DDDTooltip dichlorodiphenyldichloroethane 4 4 dichlorodiphenyldichloroethane and is also known as 2 4 dichlorodiphenyl 2 2 dichloroethane o p DDD 7 MitotaneClinical dataTrade namesLysodrenOther names1 1 Dichlorodiphenyl 2 2 dichloroethane o p DDDAHFS Drugs comMonographMedlinePlusa608050License dataUS DailyMed MitotaneRoutes ofadministrationBy mouthATC codeL01XX23 WHO Legal statusLegal statusCA only 2 US WARNING 1 In general Prescription only Pharmacokinetic dataBioavailability40 Protein binding6 Elimination half life18 159 daysIdentifiersIUPAC name RS 1 chloro 2 2 2 dichloro 1 4 chlorophenyl ethyl benzeneCAS Number53 19 0 YPubChem CID4211IUPHAR BPS6957DrugBankDB00648 YChemSpider4066 YUNII78E4J5IB5JKEGGD00420 YChEMBLChEMBL1670 YCompTox Dashboard EPA DTXSID9020372ECHA InfoCard100 000 152Chemical and physical dataFormulaC 14H 10Cl 4Molar mass320 03 g mol 13D model JSmol Interactive imageChiralityRacemic mixtureMelting point76 to 78 C 169 to 172 F SMILES Clc1ccccc1C c2ccc Cl cc2 C Cl ClInChI InChI 1S C14H10Cl4 c15 10 7 5 9 6 8 10 13 14 17 18 11 3 1 2 4 12 11 16 h1 8 13 14H YKey JWBOIMRXGHLCPP UHFFFAOYSA N Y verify Contents 1 Medical uses 2 Side effects 3 Pharmacology 3 1 Pharmacodynamics 4 Chemistry 5 History 6 Society and culture 6 1 Generic names 6 2 Brand names 7 Veterinary use 8 References 9 Further reading 10 External linksMedical uses editMitotane 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 8 The drug is also sometimes used in the treatment of Cushing s syndrome 5 Side effects editThe use of mitotane is unfortunately limited by side effects 9 which as reported by Schteinberg et al include anorexia and nausea 88 diarrhea 38 vomiting 23 decreased memory and ability to concentrate 50 rash 23 gynecomastia 50 arthralgia 19 and leukopenia 7 10 Pharmacology editPharmacodynamics edit Mitotane is an inhibitor of the adrenal cortex It acts as an inhibitor of cholesterol side chain cleavage enzyme P450scc CYP11A1 and also of 11b hydroxylase CYP11B1 18 hydroxylase aldosterone synthase CYP11B2 and 3b hydroxysteroid dehydrogenase 3b HSD to a lesser extent 3 9 In addition mitotane has direct and selective cytotoxic effects on the adrenal cortex via an unknown mechanism and thereby induces permanent adrenal atrophy similarly to DDD 11 12 Chemistry editAnalogues of mitotane include aminoglutethimide amphenone B and metyrapone History editMitotane was introduced in 1960 for the treatment of adrenocortical carcinoma 5 Society and culture editGeneric names edit Mitotane is the generic name of the medication and its INNTooltip International Nonproprietary Name USANTooltip United States Adopted Name BANTooltip British Approved Name and JANTooltip Japanese Accepted Name 6 13 Brand names edit Mitotane is sold under the brand name Lysodren 6 Veterinary use editMitotane is also used to treat Cushing s disease pituitary dependent Cushing s syndrome in dogs The medication is used in the controlled destruction of adrenal tissue leading to a decrease in cortisol production 14 References edit FDA sourced list of all drugs with black box warnings Use Download Full Results and View Query links nctr crs fda gov FDA Retrieved 22 Oct 2023 Product monograph brand safety updates Health Canada 7 July 2016 Retrieved 3 April 2024 a b Cavagnini F Giraldi FP 18 May 2010 Adrenal Causes of Hypercortisolism In Jameson JL De Groot LJ eds Endocrinology E Book Adult and Pediatric Elsevier Health Sciences pp 1888 ISBN 978 1 4557 1126 0 Hahner S Fassnacht M April 2005 Mitotane for adrenocortical carcinoma treatment Current Opinion in Investigational Drugs 6 4 386 394 PMID 15898346 a b c Dang C Trainer PJ 1 October 2010 Medical Management of Cushing s Syndrome In Bronstein MD ed Cushing s Syndrome Pathophysiology Diagnosis and Treatment Springer Science amp Business Media pp 156 ISBN 978 1 60327 449 4 a b c Elks J 14 November 2014 The Dictionary of Drugs Chemical Data Chemical Data Structures and Bibliographies Springer pp 382 ISBN 978 1 4757 2085 3 Mitotane PubChem U S National Library of Medicine Terzolo M Angeli A Fassnacht M Daffara F Tauchmanova L Conton PA et al June 2007 Adjuvant mitotane treatment for adrenocortical carcinoma The New England Journal of Medicine 356 23 2372 2380 doi 10 1056 NEJMoa063360 hdl 2318 37317 PMID 17554118 a b Tzanela M Vassiliadi DA Tsagarakis S 24 March 2014 Coincidental adrenal masses and adrenal cancer In Harris PE Bouloux PM eds Endocrinology in Clinical Practice Second ed CRC Press pp 216 ISBN 978 1 84184 951 5 Schteingart DE Motazedi A Noonan RA Thompson NW September 1982 Treatment of adrenal carcinomas Archives of Surgery 117 9 1142 1146 doi 10 1001 archsurg 1982 01380330010004 PMID 7115060 Sojka WS Raizer J 28 September 2011 Neurologic Complications of Hormonal Chemotherapies In Lee EQ Schiff D Wen PY eds Neurologic Complications of Cancer Therapy Demos Medical Publishing pp 179 ISBN 978 1 61705 019 0 Kannan CR 6 December 2012 Cushing s Syndrome The Adrenal Gland Springer Science amp Business Media pp 160 ISBN 978 1 4613 1001 3 Index Nominum 2000 International Drug Directory Taylor amp Francis 2000 pp 697 ISBN 978 3 88763 075 1 Nichols R Canine Cushing s Syndrome Diagnosis and Treatment Part 1 Typical Atypical and Pseudo Cushing s Disease PDF Archived from the original PDF on 2007 10 21 Further reading editKomissarenko VP Chelnakova IS Mikosha AS 1978 Effect of o p dichlorodiphenyldichloroethane and perthane in vitro on glutathione reductase activity in the adrenals of dogs and guinea pigs Bulletin of Experimental Biology and Medicine 85 2 152 154 doi 10 1007 BF00800110 S2CID 23181221 External links edit Mitotane information sheet Government of Canada 2017 10 16 RISK MANAGEMENT SCOPE for Benzene 1 chloro 2 2 2 dichloro 1 4 chlorophenyl ethyl Mitotane PDF Environment Canada amp Health Canada July 2013 Archived from the original PDF on 10 August 2014 Retrieved from https en wikipedia org w index php title Mitotane amp oldid 1216992640, wikipedia, wiki, book, books, library,

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