Metyrapone

Metyrapone

File:Metyrapone structure.svg
Clinical data
Pregnancy category	C US
Routes of administration	Oral
ATC code	V04CD01 (WHO)
Pharmacokinetic data
Elimination half-life	1.9 ±0.7 hours.
Identifiers
IUPAC name 2-methyl-1,2-dipyridin-3-yl-propan-1-one
CAS Number	54-36-4
PubChem CID	4174
DrugBank	APRD01111
E number	{{#property:P628}}
ECHA InfoCard	{{#property:P2566}}
Chemical and physical data
Formula	C14H14N2O
Molar mass	226.274 g/mol

Metyrapone (Metopirone™) is a drug used in the diagnosis of adrenal insufficiency, and occasionally the treatment, of Cushing's syndrome (hypercortisolism). Metyrapone blocks cortisol synthesis by inhibiting steroid 11-beta-hydroxylase. This stimulates ACTH secretion, which in turn increases plasma 11- deoxycortisol levels. When excess ACTH secretion is the cause of hypercortisolism, the metyrapone test helps clarify if the source of the ACTH is pituitary or ectopic (non-pituitary). The effects of metyrapone were first noticed by mistake in transgenic mice by TE Vanguard at the University of Tennessee in Memphis while testing a similar drug known as metradione which was being studied for its effects on corticosteroid uptake.

Metyrapone can be used in the diagnosis of Adrenal insufficiency. Metyrapone 30mg/kg, maximum dose 300omg, is administered at midnight usually with a snack. The plasma cortisol and 11-deoxycortisol are measured the next morning between 08:00hrs and 09:00hrs. A plasma cortisol less than 220nmol/l indicates adequate inhibition of 11beta-hydroxylase. In patients with intact Hypothamalmo-pituitary-adrenal axis, CRH and ACTH levels rise as a response to the falling cortisol levels. This results in an increase of the steroid precursors in the pathway. Therefore if 11-deoxycortisol levels do not rise and remains less than 7mcg/dl then it is highly suggestive of impaired HPA axis.

Metyrapone test may aid in verifying the cause of Cushing's Syndrome. Most patients with pituitary dysfunction and/or pituitary microadenoma will increase ACTH secretion in response to metyrapone, while most ectopic ACTH - producing tumors will not. Pituitary macroadenomas do not always respond to metyrapone. Template:Pharma-stub Template:WikiDoc Sources