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Identification
NameParamethasone
Accession NumberDB01384
Typesmall molecule
Groupsapproved
Description

A glucocorticoid with the general properties of corticosteroids. It has been used by mouth in the treatment of all conditions in which corticosteroid therapy is indicated except adrenal-deficiency states for which its lack of sodium-retaining properties makes it less suitable than hydrocortisone with supplementary fludrocortisone. (From Martindale, The Extra Pharmacopoeia, 30th ed, p737)

Structure
Thumb
SynonymsNot Available
SaltsNot Available
Brand names
NameCompany
HaldroneNot Available
Brand mixturesNot Available
CategoriesNot Available
CAS number53-33-8
WeightAverage: 392.4611
Monoisotopic: 392.199902243
Chemical FormulaC22H29FO5
InChI KeyInChIKey=MKPDWECBUAZOHP-AFYJWTTESA-N
InChI
InChI=1S/C22H29FO5/c1-11-6-14-13-8-16(23)15-7-12(25)4-5-20(15,2)19(13)17(26)9-21(14,3)22(11,28)18(27)10-24/h4-5,7,11,13-14,16-17,19,24,26,28H,6,8-10H2,1-3H3/t11-,13+,14+,16+,17+,19-,20+,21+,22+/m1/s1
IUPAC Name
(1S,2R,8S,10S,11S,13R,14R,15S,17S)-8-fluoro-14,17-dihydroxy-14-(2-hydroxyacetyl)-2,13,15-trimethyltetracyclo[8.7.0.0^{2,7}.0^{11,15}]heptadeca-3,6-dien-5-one
SMILES
[H][C@@]12C[C@@H](C)[C@](O)(C(=O)CO)[C@@]1(C)C[C@H](O)[C@@]1([H])[C@@]2([H])C[C@]([H])(F)C2=CC(=O)C=C[C@]12C
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassLipids
ClassSteroids and Steroid Derivatives
SubclassGluco/mineralocorticoids, Progestogins and Derivatives
Direct parentGluco/mineralocorticoids, Progestogins and Derivatives
Alternative parentsKetosteroids; Hydroxysteroids; Halogenated Steroids; Iridoids and Derivatives; Cyclohexanols; Tertiary Alcohols; Ketones; Cyclic Alcohols and Derivatives; Enolates; Polyamines; Primary Alcohols; Organofluorides; Alkyl Fluorides; Aldehydes
Substituents11-hydroxy-steroid; 6-halo-steroid; 17-hydroxy-steroid; 3-keto-steroid; 20-keto-steroid; monoterpene; 11-noriridane monoterpene; cyclohexanol; tertiary alcohol; cyclic alcohol; secondary alcohol; ketone; polyamine; enolate; primary alcohol; organofluoride; organohalogen; alcohol; carbonyl group; alkyl halide; alkyl fluoride; aldehyde
Classification descriptionThis compound belongs to the gluco/mineralocorticoids, progestogins and derivatives. These are steroids whose structure is based on an hydroxylated prostane moiety.
Pharmacology
IndicationFor the treatment of all conditions in which corticosteroid therapy is indicated except adrenal-deficiency states for which its lack of sodium-retaining properties makes it less suitable than hydrocortisone with supplementary fludrocortisone.
PharmacodynamicsParamethasone is a glucocorticoid with the general properties of corticosteroids. Glucocorticoids are a class of steroid hormones characterised by an ability to bind with the cortisol receptor and trigger a variety of important cardiovascular, metabolic, immunologic and homeostatic effects. Glucocorticoids are distinguished from mineralocorticoids and sex steroids by having different receptors, target cells, and effects. Technically, the term corticosteroid refers to both glucocorticoids and mineralocorticoids, but is often used as a synonym for glucocorticoid. Glucocorticoids suppress cell-mediated immunity. They act by inhibiting genes that code for the cytokines IL-1, IL-2, IL-3, IL-4, IL-5, IL-6, IL-8 and TNF-alpha, the most important of which is the IL-2. Reduced cytokine production limits T cell proliferation. Glucocorticoids also suppress humoral immunity, causing B cells to express lower amounts of IL-2 and IL-2 receptors. This diminishes both B cell clonal expansion and antibody synthesis. The diminished amounts of IL-2 also leads to fewer T lymphocyte cells being activated.
Mechanism of actionGlucocorticoids such as paramethasone can inhibit leukocyte infiltration at the site of inflammation, interfere with mediators of inflammatory response, and suppress humoral immune responses. The antiinflammatory actions of glucocorticoids are thought to involve phospholipase A2 inhibitory proteins, lipocortins, which control the biosynthesis of potent mediators of inflammation such as prostaglandins and leukotrienes. Paramethasone reduces inflammatory reaction by limiting the capillary dilatation and permeability of the vascular structures. These compounds restrict the accumulation of polymorphonuclear leukocytes and macrophages and reduce the release of vasoactive kinins. Recent research suggests that corticosteroids may inhibit the release of arachidonic acid from phospholipids, thereby reducing the formation of prostaglandins. Prednisolone is a glucocorticoid receptor agonist. On binding, the corticoreceptor-ligand complex translocates itself into the cell nucleus, where it binds to many glucocorticoid response elements (GRE) in the promoter region of the target genes. The DNA bound receptor then interacts with basic transcription factors, causing an increase or decrease in expression of specific target genes, including suppression of IL2 (interleukin 2) expression.
AbsorptionNot Available
Volume of distributionNot Available
Protein binding80%
Metabolism

Hepatic.

Route of eliminationCorticosteroids are metabolized primarily in the liver and are then excreted by the kidneys. Some of the topical corticosteroids and their metabolites are also excreted into the bile.
Half lifeNot Available
ClearanceNot Available
ToxicitySide effects include inhibition of bone formation, suppression of calcium absorption delayed wound healing, immune suppression, and hyperglycemia.
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption + 0.9948
Blood Brain Barrier + 0.971
Caco-2 permeable + 0.747
P-glycoprotein substrate Substrate 0.7725
P-glycoprotein inhibitor I Non-inhibitor 0.7629
P-glycoprotein inhibitor II Non-inhibitor 0.9002
Renal organic cation transporter Non-inhibitor 0.8405
CYP450 2C9 substrate Non-substrate 0.8789
CYP450 2D6 substrate Non-substrate 0.9031
CYP450 3A4 substrate Substrate 0.6991
CYP450 1A2 substrate Non-inhibitor 0.9313
CYP450 2C9 substrate Non-inhibitor 0.9254
CYP450 2D6 substrate Non-inhibitor 0.939
CYP450 2C19 substrate Non-inhibitor 0.9234
CYP450 3A4 substrate Non-inhibitor 0.7563
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.8979
Ames test Non AMES toxic 0.8509
Carcinogenicity Non-carcinogens 0.9232
Biodegradation Not ready biodegradable 1.0
Rat acute toxicity 2.3293 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.9794
hERG inhibition (predictor II) Non-inhibitor 0.6022
Pharmacoeconomics
Manufacturers
  • Eli lilly and co
PackagersNot Available
Dosage forms
FormRouteStrength
TabletOral
PricesNot Available
PatentsNot Available
Properties
Statesolid
Experimental PropertiesNot Available
Predicted Properties
PropertyValueSource
water solubility1.45e-01 g/lALOGPS
logP1.51ALOGPS
logP1.3ChemAxon
logS-3.4ALOGPS
pKa (strongest acidic)12.45ChemAxon
pKa (strongest basic)-2.9ChemAxon
physiological charge0ChemAxon
hydrogen acceptor count5ChemAxon
hydrogen donor count3ChemAxon
polar surface area94.83ChemAxon
rotatable bond count2ChemAxon
refractivity102.79ChemAxon
polarizability40.84ChemAxon
number of rings4ChemAxon
bioavailability1ChemAxon
rule of fiveYesChemAxon
Ghose filterYesChemAxon
Veber's ruleNoChemAxon
MDDR-like ruleNoChemAxon
Spectra
SpectraNot Available
References
Synthesis ReferenceNot Available
General ReferenceNot Available
External Links
ResourceLink
KEGG CompoundC07413
PubChem Compound5875
PubChem Substance46504651
ChemSpider5664
Therapeutic Targets DatabaseDAP000422
PharmGKBPA164777035
WikipediaParamethasone
ATC CodesH02AB05
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug Interactions
Drug
Acetylsalicylic acidThe corticosteroid, paramethasone, may decrease the effect of the salicylate, acetylsalicylic acid.
FosphenytoinThe enzyme inducer, fosphenytoin, may decrease the effect of the corticosteroid, paramethasone.
MidodrineIncreased arterial pressure
PhenobarbitalThe barbiturate, phenobarbital, may decrease the effect of the corticosteroid, paramethasone.
PhenytoinThe enzyme inducer, phenytoin, may decrease the effect of the corticosteroid, paramethasone.
PrimidoneThe barbiturate, primidone, may decrease the effect of the corticosteroid, paramethasone.
PyridostigmineThe corticosteroid, paramethasone, may decrease the effect of the anticholinesterase, pyridostigmine.
RifampicinThe enzyme inducer, rifampin, may decrease the effect of the corticosteroid, paramethasone.
Food InteractionsNot Available

1. Glucocorticoid receptor

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: agonist

Components

Name UniProt ID Details
Glucocorticoid receptor P04150 Details

References:

  1. Fitzgerald P, O’Brien SM, Scully P, Rijkers K, Scott LV, Dinan TG: Cutaneous glucocorticoid receptor sensitivity and pro-inflammatory cytokine levels in antidepressant-resistant depression. Psychol Med. 2006 Jan;36(1):37-43. Epub 2005 Oct 28. Pubmed
  2. Grossman R, Yehuda R, Golier J, McEwen B, Harvey P, Maria NS: Cognitive effects of intravenous hydrocortisone in subjects with PTSD and healthy control subjects. Ann N Y Acad Sci. 2006 Jul;1071:410-21. Pubmed
  3. Rautanen A, Eriksson JG, Kere J, Andersson S, Osmond C, Tienari P, Sairanen H, Barker DJ, Phillips DI, Forsen T, Kajantie E: Associations of body size at birth with late-life cortisol concentrations and glucose tolerance are modified by haplotypes of the glucocorticoid receptor gene. J Clin Endocrinol Metab. 2006 Nov;91(11):4544-51. Epub 2006 Aug 8. Pubmed
  4. Hammer F, Stewart PM: Cortisol metabolism in hypertension. Best Pract Res Clin Endocrinol Metab. 2006 Sep;20(3):337-53. Pubmed
  5. Shaw JR, Gabor K, Hand E, Lankowski A, Durant L, Thibodeau R, Stanton CR, Barnaby R, Coutermarsh B, Karlson KH, Sato JD, Hamilton JW, Stanton BA: Role of glucocorticoid receptor in acclimation of killifish (Fundulus heteroclitus) to seawater and effects of arsenic. Am J Physiol Regul Integr Comp Physiol. 2007 Feb;292(2):R1052-60. Epub 2006 Oct 12. Pubmed
  6. Sher L: Combined dexamethasone suppression-corticotropin-releasing hormone stimulation test in studies of depression, alcoholism, and suicidal behavior. ScientificWorldJournal. 2006 Oct 31;6:1398-404. Pubmed

1. Cytochrome P450 3A4

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate inhibitor

Components

Name UniProt ID Details
Cytochrome P450 3A4 P08684 Details

References:

  1. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
  2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed
  3. Ekins S, Bravi G, Wikel JH, Wrighton SA: Three-dimensional-quantitative structure activity relationship analysis of cytochrome P-450 3A4 substrates. J Pharmacol Exp Ther. 1999 Oct;291(1):424-33. Pubmed

1. Corticosteroid-binding globulin

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: binder

Components

Name UniProt ID Details
Corticosteroid-binding globulin P08185 Details

References:

  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
  3. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

Comments
Drug created on July 06, 2007 14:34 / Updated on September 16, 2013 17:14