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. It is a derivative of the early

insecticide Insecticides are substances used to kill insects. They include ovicides and larvicides used against insect eggs and larvae, respectively. Insecticides are used in agriculture, medicine, industry and by consumers. Insecticides are claimed to b ...

DDT and an

isomer In chemistry, isomers are molecules or polyatomic ions with identical molecular formulae – that is, same number of atoms of each element – but distinct arrangements of atoms in space. Isomerism is existence or possibility of isomers. Iso ...

of (4,4'-dichlorodiphenyldichloroethane) and is also known as 2,4'-(dichlorodiphenyl)-2,2-dichloroethane (o,p'-DDD).Information from PubChem
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Medical uses

Mitotane has been produced by

Bristol Myers Squibb The Bristol Myers Squibb Company (BMS) is an American multinational pharmaceutical company. Headquartered in New York City, BMS is one of the world's largest pharmaceutical companies and consistently ranks on the ''Fortune'' 500 list of the lar ...

but it is marketed as an

orphan drug An orphan drug is a pharmaceutical agent developed to treat medical conditions which, because they are so rare, would not be profitable to produce without government assistance. The conditions are referred to as orphan diseases. The assignment of ...

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. The drug is also sometimes used in the treatment of Cushing's syndrome.

Side effects

The use of mitotane is unfortunately limited by side effects, 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%).

Pharmacology

Pharmacodynamics

Mitotane is an inhibitor of the

adrenal cortex The adrenal cortex is the outer region and also the largest part of an adrenal gland. It is divided into three separate zones: zona glomerulosa, zona fasciculata and zona reticularis. Each zone is responsible for producing specific hormones. It is ...

. It acts as an

inhibitor Inhibitor or inhibition may refer to: In biology * Enzyme inhibitor, a substance that binds to an enzyme and decreases the enzyme's activity * Reuptake inhibitor, a substance that increases neurotransmission by blocking the reuptake of a neurotra ...

of cholesterol side-chain cleavage enzyme (P450scc, CYP11A1), and also of 11β-hydroxylase (CYP11B1),

18-hydroxylase Aldosterone synthase, also called steroid 18-hydroxylase, corticosterone 18-monooxygenase or P450C18, is a steroid hydroxylase cytochrome P450 enzyme involved in the biosynthesis of the mineralocorticoid aldosterone and other steroids. The enzyme ...

(aldosterone synthase, CYP11B2), and 3β-hydroxysteroid dehydrogenase (3β-HSD) to a lesser extent. In addition, mitotane has direct and selective

cytotoxic Cytotoxicity is the quality of being toxic to cells. Examples of toxic agents are an immune cell or some types of venom, e.g. from the puff adder (''Bitis arietans'') or brown recluse spider (''Loxosceles reclusa''). Cell physiology Treating cells ...

effects on the adrenal cortex, via an unknown mechanism, and thereby induces permanent adrenal atrophy similarly to DDD.

Chemistry

Analogues of mitotane include

aminoglutethimide Aminoglutethimide (AG), sold under the brand names Elipten, Cytadren, and Orimeten among others, is a medication which has been used in the treatment of seizures, Cushing's syndrome, breast cancer, and prostate cancer, among other indications. ...

amphenone B Amphenone B, or simply amphenone, also known as 3,3-bis(''p''-aminophenyl)butan-2-one, is an inhibitor of steroid hormone and thyroid hormone biosynthesis which was never marketed but has been used as a tool in scientific research to study corti ...

, and

metyrapone Metyrapone, sold under the brand name Metopirone, is a medication which is used in the diagnosis of adrenal insufficiency and occasionally in the treatment of Cushing's syndrome (hypercortisolism). Medical uses Metyrapone can be used in the dia ...

History

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

Society and culture

Generic names

''Mitotane'' is the generic name of the drug and its , , , and .

Brand names

Mitotane has been sold under the brand name Lysodren.

Veterinary use

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.Canine Cushing’s Syndrome: Diagnosis and Treatment

References

External links

* * Government of Canada:
Benzene, 1-chloro-2-[2,2-dichloro-1-(4-chlorophenyl)ethyl]- (Mitotane)
' * Environment Canada & Health Canada:
RISK MANAGEMENT SCOPE for Benzene, 1-chloro-2-[2,2-dichloro-1-(4-chlorophenyl)ethyl]- (Mitotane)
', 2013 {{Glucocorticoids and antiglucocorticoids 3β-Hydroxysteroid dehydrogenase inhibitors 11β-Hydroxylase inhibitors Aldosterone synthase inhibitors Antiglucocorticoids Antineoplastic drugs Chloroarenes Cholesterol side-chain cleavage enzyme inhibitors CYP3A4 inducers Organochlorides Orphan drugs