NAV

Paramethasone

Identification

Generic Name
Paramethasone
DrugBank Accession Number
DB01384
Background

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)

Type
Small Molecule
Groups
Experimental
Structure
3D
Similar Structures
Weight
Average: 392.4611
Monoisotopic: 392.199902243
Chemical Formula
C22H29FO5
Synonyms
  • Parametasona
  • Parametasone
  • Paramethasone
  • Paramethasonum
External IDs
  • CS 1483
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Pharmacology

Indication

For 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.

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Contraindications & Blackbox Warnings
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Pharmacodynamics

Paramethasone 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 action

Glucocorticoids 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.

TargetActionsOrganism
AGlucocorticoid receptor
agonist
Humans
Absorption

Not Available

Volume of distribution

Not Available

Protein binding

80%

Metabolism

Hepatic.

Route of elimination

Corticosteroids 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-life

Not Available

Clearance

Not Available

Adverse Effects
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Toxicity

Side effects include inhibition of bone formation, suppression of calcium absorption delayed wound healing, immune suppression, and hyperglycemia.

Pathways
Not Available
Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
Not Available

Interactions

Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
Integrate drug-drug
interactions in your software
AbametapirThe serum concentration of Paramethasone can be increased when it is combined with Abametapir.
AbataceptThe risk or severity of adverse effects can be increased when Abatacept is combined with Paramethasone.
AbemaciclibThe metabolism of Abemaciclib can be increased when combined with Paramethasone.
AcalabrutinibThe metabolism of Acalabrutinib can be increased when combined with Paramethasone.
AcarboseThe risk or severity of hyperglycemia can be increased when Paramethasone is combined with Acarbose.
Food Interactions
Not Available

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International/Other Brands
Dillar

Categories

ATC Codes
H02AB05 — Paramethasone
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as 21-hydroxysteroids. These are steroids carrying a hydroxyl group at the 21-position of the steroid backbone.
Kingdom
Organic compounds
Super Class
Lipids and lipid-like molecules
Class
Steroids and steroid derivatives
Sub Class
Hydroxysteroids
Direct Parent
21-hydroxysteroids
Alternative Parents
Gluco/mineralocorticoids, progestogins and derivatives / 20-oxosteroids / 11-beta-hydroxysteroids / 17-hydroxysteroids / 3-oxo delta-1,4-steroids / Halogenated steroids / Delta-1,4-steroids / Tertiary alcohols / Alpha-hydroxy ketones / Secondary alcohols
show 7 more
Substituents
11-beta-hydroxysteroid / 11-hydroxysteroid / 17-hydroxysteroid / 20-oxosteroid / 21-hydroxysteroid / 3-oxo-delta-1,4-steroid / 3-oxosteroid / 6-halo-steroid / Alcohol / Aliphatic homopolycyclic compound
show 21 more
Molecular Framework
Aliphatic homopolycyclic compounds
External Descriptors
fluorinated steroid (CHEBI:7922)
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
VFC6ZX3584
CAS number
53-33-8
InChI Key
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
(1R,2R,3aS,3bS,5S,9aR,9bS,10S,11aS)-5-fluoro-1,10-dihydroxy-1-(2-hydroxyacetyl)-2,9a,11a-trimethyl-1H,2H,3H,3aH,3bH,4H,5H,7H,9aH,9bH,10H,11H,11aH-cyclopenta[a]phenanthren-7-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

References

General References
Not Available
Human Metabolome Database
HMDB0015462
KEGG Drug
D07464
KEGG Compound
C07413
PubChem Compound
5875
PubChem Substance
46504651
ChemSpider
5664
RxNav
7910
ChEBI
7922
ChEMBL
CHEMBL1579
ZINC
ZINC000004097384
Therapeutic Targets Database
DAP000422
PharmGKB
PA164777035
Wikipedia
Paramethasone

Clinical Trials

Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
PhaseStatusPurposeConditionsCount

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.145 mg/mLALOGPS
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 Area94.83 Å2Chemaxon
Rotatable Bond Count2Chemaxon
Refractivity102.79 m3·mol-1Chemaxon
Polarizability40.81 Å3Chemaxon
Number of Rings4Chemaxon
Bioavailability1Chemaxon
Rule of FiveYesChemaxon
Ghose FilterYesChemaxon
Veber's RuleNoChemaxon
MDDR-like RuleNoChemaxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+0.9948
Blood Brain Barrier+0.971
Caco-2 permeable+0.747
P-glycoprotein substrateSubstrate0.7725
P-glycoprotein inhibitor INon-inhibitor0.7629
P-glycoprotein inhibitor IINon-inhibitor0.9002
Renal organic cation transporterNon-inhibitor0.8405
CYP450 2C9 substrateNon-substrate0.8789
CYP450 2D6 substrateNon-substrate0.9031
CYP450 3A4 substrateSubstrate0.6991
CYP450 1A2 substrateNon-inhibitor0.9313
CYP450 2C9 inhibitorNon-inhibitor0.9254
CYP450 2D6 inhibitorNon-inhibitor0.939
CYP450 2C19 inhibitorNon-inhibitor0.9234
CYP450 3A4 inhibitorNon-inhibitor0.7563
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8979
Ames testNon AMES toxic0.8509
CarcinogenicityNon-carcinogens0.9232
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.3293 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9794
hERG inhibition (predictor II)Non-inhibitor0.6022
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSsplash10-0ab9-4889000000-fdfca86534eb8016e0ab
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-0a6r-0009000000-e95a1eeed7d71bff5507
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-03di-0009000000-de18d1f3f74904d0061a
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-06vi-0179000000-7d657f6efbc7fabb5475
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-052f-9007000000-a6516a354ba773fdf4cc
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-00m0-0961000000-3069fd36e169e5dfec97
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-0006-0009000000-c6f2bffe6a91b06ea905
Predicted 1H NMR Spectrum1D NMRNot Applicable
Predicted 13C NMR Spectrum1D NMRNot Applicable
Chromatographic Properties
Collision Cross Sections (CCS)
AdductCCS Value (Å2)Source typeSource
[M-H]-194.8687403
predicted
DarkChem Lite v0.1.0
[M-H]-188.74069
predicted
DeepCCS 1.0 (2019)
[M+H]+196.7731403
predicted
DarkChem Lite v0.1.0
[M+H]+190.60094
predicted
DeepCCS 1.0 (2019)
[M+Na]+195.1418403
predicted
DarkChem Lite v0.1.0
[M+Na]+196.99733
predicted
DeepCCS 1.0 (2019)

Targets

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insights and accelerate drug research.
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Details1. Glucocorticoid receptor
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Agonist
General Function
Zinc ion binding
Specific Function
Receptor for glucocorticoids (GC). Has a dual mode of action: as a transcription factor that binds to glucocorticoid response elements (GRE), both for nuclear and mitochondrial DNA, and as a modula...
Gene Name
NR3C1
Uniprot ID
P04150
Uniprot Name
Glucocorticoid receptor
Molecular Weight
85658.57 Da
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. [Article]
  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. [Article]
  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. [Article]
  4. Hammer F, Stewart PM: Cortisol metabolism in hypertension. Best Pract Res Clin Endocrinol Metab. 2006 Sep;20(3):337-53. [Article]
  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. [Article]
  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. [Article]

Enzymes

Details1. Cytochrome P450 3A4
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
Inducer
Curator comments
Induction likely occurs indirectly due to transcriptional modulation via the glucocorticoid receptor.
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. 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. [Article]
  2. Dvorak Z, Pavek P: Regulation of drug-metabolizing cytochrome P450 enzymes by glucocorticoids. Drug Metab Rev. 2010 Nov;42(4):621-35. doi: 10.3109/03602532.2010.484462. [Article]
  3. Flockhart Table of Drug Interactions [Link]
Details2. Cytochrome P450 3A5
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inducer
General Function
Oxygen binding
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP3A5
Uniprot ID
P20815
Uniprot Name
Cytochrome P450 3A5
Molecular Weight
57108.065 Da
References
  1. Dvorak Z, Pavek P: Regulation of drug-metabolizing cytochrome P450 enzymes by glucocorticoids. Drug Metab Rev. 2010 Nov;42(4):621-35. doi: 10.3109/03602532.2010.484462. [Article]

Carriers

Details1. Corticosteroid-binding globulin
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Binder
General Function
Steroid binding
Specific Function
Major transport protein for glucocorticoids and progestins in the blood of almost all vertebrate species.
Gene Name
SERPINA6
Uniprot ID
P08185
Uniprot Name
Corticosteroid-binding globulin
Molecular Weight
45140.49 Da
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. [Article]
  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. [Article]
  3. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]

Drug created at July 06, 2007 20:34 / Updated at February 21, 2021 18:51