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Identification
NameCorticotropin
Accession NumberDB01285
Typebiotech
Groupsapproved
Description

Corticotropin (ACTH or adrenocorticotropic hormone) is a polypeptide hormone produced and secreted by the pituitary gland. It is an important player in the hypothalamic-pituitary-adrenal axis.

Protein structureNo structure small
Protein chemical formulaC207H308N56O58S
Protein average weight4541.0658
Sequences
>ACTH(1-39)
SYSMEHFRWGKPVGKKRRPVKVYPDGAEDQLAEAFPLEF
Download FASTA Format
Synonyms
SynonymLanguageCode
ACTHNot AvailableNot Available
Adrenocorticotropic hormoneNot AvailableNot Available
SaltsNot Available
Brand names
NameCompany
Acthar GelNot Available
Brand mixturesNot Available
Categories
CAS number9002-60-2
Taxonomy
KingdomOrganic Compounds
SuperclassOrganic Acids
ClassCarboxylic Acids and Derivatives
SubclassAmino Acids, Peptides, and Analogues
Direct parentPeptides
Alternative parentsNot Available
SubstituentsNot Available
Classification descriptionNot Available
Pharmacology
IndicationFor use as a diagnostic agent in the screening of patients presumed to have adrenocortical insufficiency.
PharmacodynamicsCorticotropin acts through the stimulation of cell surface ACTH receptors, which are primarily located on the adrenocortical cells. Corticotropin stimulates the cortex of the adrenal gland and boosts the synthesis of corticosteroids, mainly glucocorticoids but also sex steroids (androgens). Corticotropin is also related to the circadian rhythm in many organisms.
Mechanism of actionAs a diagnostic aid (adrenocortical function), corticotropin combines with a specific receptor on the adrenal cell plasma membrane. In patients with normal adrenocortical function, it stimulates the initial reaction involved in the synthesis of adrenal steroids (including cortisol, cortisone, weak androgenic substances, and a limited quantity of aldosterone) from cholesterol by increasing the quantity of cholesterol within the mitochondria. Corticotropin does not significantly increase serum cortisol concentrations in patients with primary adrenocortical insufficiency (Addison's disease). The mechanism of action of corticotropin in the treatment of infantile myoclonic seizures is unknown.
AbsorptionCorticotropin is rapidly absorbed following intramuscular administration; the repository dosage form is slowly absorbed over approximately 8 to 16 hours.
Volume of distributionNot Available
Protein bindingNot Available
Metabolism
Route of eliminationNot Available
Half lifeAbout 15 minutes following intravenous administration.
ClearanceNot Available
ToxicityNot Available
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
Pharmacoeconomics
Manufacturers
  • Parkedale pharmaceuticals inc
  • Sanofi aventis us llc
  • Organics lagrange inc
  • Watson laboratories inc
  • Questcor pharmaceuticals inc
  • Organon usa inc
  • Armour pharmaceutical co
Packagers
Dosage formsNot Available
Prices
Unit descriptionCostUnit
Acthar hp gel 80 unit/ml vial5584.56USDml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
PatentsNot Available
Properties
Statesolid
Experimental Properties
PropertyValueSource
water solubilityEasily soluble in cold water, hot water.Not Available
References
Synthesis Reference

Wylie W. Vale, Jr., Mary P. Stenzel-Poore, “Corticotropin-releasing factor overproducing transgenic mice.” U.S. Patent US6023011, issued June, 1993.

US6023011
General ReferenceNot Available
External Links
ResourceLink
PharmGKBPA449129
Drugs.comhttp://www.drugs.com/cdi/corticotropin-gel.html
WikipediaAdrenocorticotropic_hormone
ATC CodesH01AA01
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSshow(72.7 KB)
Interactions
Drug Interactions
Drug
AldesleukinCorticosteroids may diminish the antineoplastic effect of Aldesleukin. Avoid conccurent use of corticosteroids with aldesleukin.
AprepitantAprepitant may increase the serum concentration of Corticosteroids (Systemic). Monitor for increased effects of systemic corticosteroids when coadmininistered with aprepitant; corticosteroid dose reduction may be necessary. The manufacturer of fosaprepitant (a prodrug of aprepitant) states that oral dexamethasone doses should be reduced by 50% when coadministered with a fosaprepitant/aprepitant regimen to achieve dexamethasone concentrations similar to those achieved with dexamethasone alone. Dexamethasone doses used in clinical chemotherapy nausea/vomiting studies with aprepitant reflect this 50% decrease. Similarly, it is recommended that in order to achieve concentrations similar to those achieved with methylprednisolone alone, the intravenous methylprednisolone dose should be reduced by 25% and the oral methylprednisolone dose should be reduced by 50% when given together with a fosaprepitant/aprepitant regimen.
FosaprepitantFosaprepitant may increase the serum concentration of Corticosteroids (Systemic). The active metabolite aprepitant is likely responsible for this effect. The manufacturer of fosaprepitant states that oral dexamethasone doses should be reduced by 50% when coadministered with a fosaprepitant/aprepitant regimen to achieve dexamethasone concentrations similar to those achieved with dexamethasone alone.1 Dexamethasone doses used in clinical chemotherapy nausea/vomiting studies with aprepitant reflect this 50% decrease. Similarly, it is recommended that in order to achieve concentrations similar to those achieved with methylprednisolone alone, the intravenous methylprednisolone dose should be reduced by 25% and the oral methylprednisolone dose should be reduced by 50% when given together with a fosaprepitant/aprepitant regimen. Monitor for increased effects of systemic corticosteroids when coadmininistered with fosaprepitant or aprepitant.
LeflunomideImmunosuppressants may enhance the adverse/toxic effect of Leflunomide. Specifically, the risk for hematologic toxicity such as pancytopenia, agranulocytosis, and/or thrombocytopenia may be increased. Consider eliminating the use of a leflunomide loading dose in patients who are receiving other immunosuppressants in order to reduce the risk for serious adverse events such as hematologic toxicity. Also, patients receiving both leflunomide and another immunosuppressive medication should be monitored for bone marrow suppression at least monthly throughout the duration of concurrent therapy.
PyridostigmineThe corticosteroid, corticotropin, may decrease the effect of the anticholinesterase, pyridostigmine.
TacrineTacrine and Corticotropin may independently exacerbate muscle weakness in myasthenia gravis patients. Monitor for additive muscle weakness effects.
TrastuzumabTrastuzumab may increase the risk of neutropenia and anemia. Monitor closely for signs and symptoms of adverse events.
VecuroniumVecuronium may increase the adverse neuromuscular effects of systemic corticosteroids, such as Corticotropin. Monitor for increased muscle weakness and signs of polyneuropathies and myopathy.
Food InteractionsNot Available

Targets

1. Adrenocorticotropic hormone receptor

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: agonist

Components

Name UniProt ID Details
Adrenocorticotropic hormone receptor Q01718 Details

References:

  1. Johnston H, King PJ, O’Shaughnessy PJ: Effects of ACTH and expression of the melanocortin-2 receptor in the neonatal mouse testis. Reproduction. 2007 Jun;133(6):1181-7. Pubmed
  2. Carey LC, Su Y, Valego NK, Rose JC: Infusion of ACTH stimulates expression of adrenal ACTH receptor and steroidogenic acute regulatory protein mRNA in fetal sheep. Am J Physiol Endocrinol Metab. 2006 Aug;291(2):E214-20. Epub 2006 Feb 14. Pubmed
  3. Hruby VJ, Cai M, Cain JP, Mayorov AV, Dedek MM, Trivedi D: Design, synthesis and biological evaluation of ligands selective for the melanocortin-3 receptor. Curr Top Med Chem. 2007;7(11):1107-19. Pubmed
  4. Suri D, Alonso M, Weiss RE: A case of ACTH-independent bilateral macronodular adrenal hyperplasia and severe congestive heart failure. J Endocrinol Invest. 2006 Nov;29(10):940-6. Pubmed
  5. Lin L, Hindmarsh PC, Metherell LA, Alzyoud M, Al-Ali M, Brain CE, Clark AJ, Dattani MT, Achermann JC: Severe loss-of-function mutations in the adrenocorticotropin receptor (ACTHR, MC2R) can be found in patients diagnosed with salt-losing adrenal hypoplasia. Clin Endocrinol (Oxf). 2007 Feb;66(2):205-10. Pubmed

2. Corticoliberin

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: agonist

Components

Name UniProt ID Details
Corticoliberin P06850 Details

References:

  1. Hellman P, Linder F, Hennings J, Hessman O, Eriksson B, Orlefors H, Akerstrom G: Bilateral adrenalectomy for ectopic Cushing’s syndrome-discussions on technique and indication. World J Surg. 2006 May;30(5):909-16. Pubmed
  2. Dinan TG, Quigley EM, Ahmed SM, Scully P, O’Brien S, O’Mahony L, O’Mahony S, Shanahan F, Keeling PW: Hypothalamic-pituitary-gut axis dysregulation in irritable bowel syndrome: plasma cytokines as a potential biomarker? Gastroenterology. 2006 Feb;130(2):304-11. Pubmed
  3. Zhao LF, Iwasaki Y, Oki Y, Tsugita M, Taguchi T, Nishiyama M, Takao T, Kambayashi M, Hashimoto K: Purinergic receptor ligands stimulate pro-opiomelanocortin gene expression in AtT-20 pituitary corticotroph cells. J Neuroendocrinol. 2006 Apr;18(4):273-8. Pubmed
  4. Wagner U, Wahle M, Moritz F, Wagner U, Hantzschel H, Baerwald CG: Promoter polymorphisms regulating corticotrophin-releasing hormone transcription in vitro. Horm Metab Res. 2006 Feb;38(2):69-75. Pubmed
  5. Matejec R, Uhlich H, Hotz C, Muhling J, Harbach HW, Bodeker RH, Hempelmann G, Teschemacher H: Corticotropin-releasing hormone reduces pressure pain sensitivity in humans without involvement of beta-endorphin(1-31), but does not reduce heat pain sensitivity. Neuroendocrinology. 2005;82(3-4):185-97. Epub 2006 Mar 13. Pubmed

Enzymes

1. 3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase type 2

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inducer

Components

Name UniProt ID Details
3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase type 2 P26439 Details

References:

  1. Bassett MH, Suzuki T, Sasano H, De Vries CJ, Jimenez PT, Carr BR, Rainey WE: The orphan nuclear receptor NGFIB regulates transcription of 3beta-hydroxysteroid dehydrogenase. implications for the control of adrenal functional zonation. J Biol Chem. 2004 Sep 3;279(36):37622-30. Epub 2004 Jun 18. Pubmed

2. 25-hydroxyvitamin D-1 alpha hydroxylase, mitochondrial

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inducer

Components

Name UniProt ID Details
25-hydroxyvitamin D-1 alpha hydroxylase, mitochondrial O15528 Details

References:

  1. Dunbar DR, Khaled H, Evans LC, Al-Dujaili EA, Mullins LJ, Mullins JJ, Kenyon CJ, Bailey MA: Transcriptional and physiological responses to chronic ACTH treatment by the mouse kidney. Physiol Genomics. 2010 Feb 4;40(3):158-66. Epub 2009 Nov 17. Pubmed

3. 1,25-dihydroxyvitamin D(3) 24-hydroxylase, mitochondrial

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inducer

Components

Name UniProt ID Details
1,25-dihydroxyvitamin D(3) 24-hydroxylase, mitochondrial Q07973 Details

References:

  1. Dunbar DR, Khaled H, Evans LC, Al-Dujaili EA, Mullins LJ, Mullins JJ, Kenyon CJ, Bailey MA: Transcriptional and physiological responses to chronic ACTH treatment by the mouse kidney. Physiol Genomics. 2010 Feb 4;40(3):158-66. Epub 2009 Nov 17. Pubmed

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Drug created on May 23, 2007 23:14 / Updated on September 13, 2013 11:05