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Identification
Name Corticotropin
Accession Number DB01285
Type biotech
Groups approved
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 structure No_structure_small
Protein chemical formula C207H308N56O58S
Protein average weight 4541.0658
Sequences 
>ACTH(1-39)
SYSMEHFRWGKPVGKKRRPVKVYPDGAEDQLAEAFPLEF

FASTA
Synonyms
ACTH
Adrenocorticotopin
Adrenocorticotropic hormone
Corticotrophin
Cortrophin
Salts Not Available
Brand names
Name Company
Acethropan
Acortan
ACTH
Acthar
Exacthin
H.P. Acthar Gel
Isactid
Purified cortrophin gel
Reacthin
Solacthyl
Tubex
First Prev Next Last
Brand mixtures Not Available
Categories
  • Diagnostic Agents
CAS number 9002-60-2
Taxonomy
Kingdom Not Available
Classes Not Available
Substructures Not Available
Pharmacology
Indication For use as a diagnostic agent in the screening of patients presumed to have adrenocortical insufficiency.
Pharmacodynamics Corticotropin 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 action As 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.
Absorption Corticotropin is rapidly absorbed following intramuscular administration; the repository dosage form is slowly absorbed over approximately 8 to 16 hours.
Volume of distribution Not Available
Protein binding Not Available
Metabolism Not Available
Route of elimination Not Available
Half life About 15 minutes following intravenous administration.
Clearance Not Available
Toxicity Not Available
Affected organisms
  • Humans and other mammals
Pathways Not 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 forms Not Available
Prices
Unit description Cost Unit
Acthar hp gel 80 unit/ml vial 5584.56 USD ml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents Not Available
Properties
State solid
Experimental Properties
Property Value Source
water solubility Easily soluble in cold water, hot water. Not Available
References
Synthesis Reference Not Available
General Reference Not Available
External Links
Resource Link
PharmGKB PA449129 Link_out
Drugs.com http://www.drugs.com/cdi/corticotropin-gel.html Link_out
Wikipedia http://en.wikipedia.org/wiki/Adrenocorticotropic_hormone Link_out
ATC Codes
  • H01AA01
AHFS Codes Not Available
PDB Entries Not Available
FDA label Not Available
MSDS show (72.7 KB)
Interactions
Drug Interactions
Drug Interaction
Aldesleukin Corticosteroids may diminish the antineoplastic effect of Aldesleukin. Avoid conccurent use of corticosteroids with aldesleukin.
Aprepitant Aprepitant 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.
Fosaprepitant Fosaprepitant 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.
Leflunomide Immunosuppressants 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.
Pyridostigmine The corticosteroid, corticotropin, may decrease the effect of the anticholinesterase, pyridostigmine.
Tacrine Tacrine and Corticotropin may independently exacerbate muscle weakness in myasthenia gravis patients. Monitor for additive muscle weakness effects.
Trastuzumab Trastuzumab may increase the risk of neutropenia and anemia. Monitor closely for signs and symptoms of adverse events.
Vecuronium Vecuronium may increase the adverse neuromuscular effects of systemic corticosteroids, such as Corticotropin. Monitor for increased muscle weakness and signs of polyneuropathies and myopathy.
Food Interactions Not Available
Targets

1. Adrenocorticotropic hormone receptor

Pharmacological action: yes
Actions: agonist

Receptor for ACTH. This receptor is mediated by G proteins (G(s)) which activate adenylate cyclase

Organism class: human
UniProt ID: Q01718 Link_out
Gene: MC2R Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Pharmacological action: unknown
Actions: agonist

This hormone from hypothalamus regulates the release of corticotropin from pituitary gland

Organism class: human
UniProt ID: P06850 Link_out
Gene: CRH Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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 II

Actions: inducer

3beta-HSD is a bifunctional enzyme, that catalyzes the oxidative conversion of delta(5)-ene-3-beta-hydroxy steroid, and the oxidative conversion of ketosteroids. The 3beta-HSD enzymatic system plays a crucial role in the biosynthesis of all classes of hormonal steroids

UniProt ID: P26439 Link_out
Gene: HSD3B2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Actions: inducer

Catalyzes the conversion of 25-hydroxyvitamin D3 (25(OH)D) to 1-alpha,25-dihydroxyvitamin D3 (1,25(OH)2D) plays an important role in normal bone growth, calcium metabolism, and tissue differentiation

UniProt ID: O15528 Link_out
Gene: CYP27B1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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. Cytochrome P450 24A1, mitochondrial

Actions: inducer

Has a role in maintaining calcium homeostasis. Catalyzes the NADPH-dependent 24-hydroxylation of 25-hydroxyvitamin D(3) in the presence of adrenodoxin and NADPH-adrenodoxin reductase

UniProt ID: Q07973 Link_out
Gene: CYP24A1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
Comments
Drug created on May 23, 2007 23:14 / Updated on May 30, 2012 21:33