Metyrapone

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Metyrapone
Metyrapone structure.svg
Systematic (IUPAC) name
2-methyl-1,2-di(pyridin-3-yl)propan-1-one
Clinical data
Trade names Metopirone
AHFS/Drugs.com Consumer Drug Information
Pregnancy cat. C US
Legal status ?
Routes Oral
Pharmacokinetic data
Half-life 1.9 ±0.7 hours.
Identifiers
CAS number 54-36-4 YesY
ATC code V04CD01
PubChem CID 4174
DrugBank DB01011
ChemSpider 4030 YesY
UNII ZS9KD92H6V YesY
KEGG D00410 YesY
ChEBI CHEBI:44241 YesY
ChEMBL CHEMBL934 YesY
Chemical data
Formula C14H14N2O 
Mol. mass 226.274 g/mol
 YesY (what is this?)  (verify)

Metyrapone (trade name Metopirone) is a drug used in the diagnosis of adrenal insufficiency and occasionally in the treatment of Cushing's syndrome (hypercortisolism).

Mechanism[edit]

Metyrapone blocks cortisol synthesis[1] by inhibiting steroid 11β-hydroxylase. This stimulates ACTH secretion, which in turn increases plasma 11-deoxycortisol levels.

Uses[edit]

Metyrapone can be used in the diagnosis of adrenal insufficiency. Metyrapone 30 mg/kg, maximum dose 3000 mg, is administered at midnight usually with a snack. The plasma cortisol and 11-deoxycortisol are measured the next morning between 8:00 and 9:00 am. A plasma cortisol less than 220 nmol/l indicates adequate inhibition of 11β-hydroxylase. In patients with intact Hypothalamo-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 7 µg/dl (202 nmol/l) and ACTH rises, then it is highly suggestive of impaired adrenal insufficiency, if neither 11-deoxycortisol nor ACTH rise it is highly suggestive of an impaired HPA axis at either the pituitary or hypothalamus.

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.

Experimental use[edit]

Metyrapone has been found in early human trials to reduce recollection of emotional memories in normal volunteers. The volunteers showed significant impairment in ability to retrieve memories with negative emotional content while not impairing memories with neutral content. This has significant implication in the study of the process of emotional healing in post traumatic stress disorder.[2][3]

Due to the permissive action of cortisol on glucagon partial blockade of cortisol may reduce the effects of circulating glucagon in chronically increasing blood glucose in Syndrome X / type 2 diabetes.

References[edit]

  1. ^ Young EA, Ribeiro SC, Ye W (June 2007). "Sex Differences in ACTH Pulsatility following Metyrapone Blockade in Patients with Major Depression". Psychoneuroendocrinology 32 (5): 503–7. doi:10.1016/j.psyneuen.2007.03.003. PMC 1975691. PMID 17462829. 
  2. ^ University of Montreal (27 May 2011). "Drug may help overwrite bad memories". Science Daily (online: ScienceDaily). Retrieved 27 May 2011. 
  3. ^ Marin, Marie-Frances; A. Hupbach, F. S. Maheu, K. Nader, S. J. Lupien. "Metyrapone Administration Reduces the Strength of an Emotional Memory Trace in a Long-Lasting Manner". Journal of Clinical Endocrinology & Metabolism. early release abstract (8): E1221. doi:10.1210/jc.2011-0226. 

See also[edit]

External links[edit]

Huffington Post reports that Metyrapone may someday by used to manage PTSD by weakening those bad memories while keeping the good ones strong.