DrugBank: Methylprednisolone (DB00959)

targets (1) enzymes (1) transporters (1)

Identification

Name

Methylprednisolone

Accession Number

DB00959 (APRD00342)

Type

small molecule

Groups

approved

Description

A prednisolone derivative with similar anti-inflammatory action. [PubChem]

Structure

Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure

Synonyms

6alpha-Methylprednisolone
Methyleneprednisolone
Methylprednisolon
Methylprednisolonum [INN-Latin]
Metilprednisolona [INN-Spanish]
Metilprednisolone [Dcit]

Brand names

Artisone-Wyeth
Besonia
Dopomedrol
Esametone
Firmacort
Lemod
Medesone
Medixon
Medlone 21
Medrate
Medrol Adt Pak
Medrol Dosepak
Medrone
Mesopren
Metastab
Metilbetasone
Metrisone
Metrocort
Metysolon
Moderin
Nirypan
Noretona
Predni N Tablinen
Promacortine
Reactenol
Sieropresol
Solomet
Summicort
Suprametil
Urbason
Urbasone
Wyacort

Brand name mixtures

Depo-Medrol with Lidocaine (Lidocaine Hydrochloride + Methylprednisolone Acetate)
Medrol Acne Lotion (Aluminum Chlorohydrate + Methylprednisolone Acetate + Sulfur)
Methylprednisolone Sodium Succinate for Injection (Methylprednisolone + Water)
Neo-Medrol (Methylprednisolone Acetate + Neomycin Sulfate)
Neo-Medrol Acne Lotion (Aluminum Chlorohydrate + Methylprednisolone Acetate + Neomycin Sulfate + Sulfur)

Categories

Anti-inflammatory Agents
Adrenergic Agents
Antiemetics
Neuroprotective Agents
Glucocorticoids

CAS number

83-43-2

Weight

Average: 374.4706
Monoisotopic: 374.209324070

Chemical Formula

C₂₂H₃₀O₅

InChI Key

InChIKey=VHRSUDSXCMQTMA-PJHHCJLFSA-N

InChI

InChI=1S/C22H30O5/c1-12-8-14-15-5-7-22(27,18(26)11-23)21(15,3)10-17(25)19(14)20(2)6-4-13(24)9-16(12)20/h4,6,9,12,14-15,17,19,23,25,27H,5,7-8,10-11H2,1-3H3/t12-,14-,15-,17-,19+,20-,21-,22-/m0/s1

Plain Text

IUPAC Name

(1S,2R,8S,10S,11S,14R,15S,17S)-14,17-dihydroxy-14-(2-hydroxyacetyl)-2,8,15-trimethyltetracyclo[8.7.0.0^{2,7}.0^{11,15}]heptadeca-3,6-dien-5-one

SMILES

[H][C@@]12CC[C@](O)(C(=O)CO)[C@@]1(C)C[C@H](O)[C@@]1([H])[C@@]2([H])C[C@H](C)C2=CC(=O)C=C[C@]12C

Plain Text

Mass Spec

Not Available

Taxonomy

Kingdom

Organic

Classes

Steroids and Steroid Derivatives

Substructures

Steroids and Steroid Derivatives
Hydroxy Compounds
Alkanes and Alkenes
Alcohols and Polyols
Ketones

Pharmacology

Indication

Adjunctive therapy for short-term administration in rheumatoid arthritis.

Pharmacodynamics

Methylprednisolone and its derivatives, methylprednisolone sodium succinate and methylprednisolone acetate, are synthetic glucocorticoids used as antiinflammatory or immunosuppressive agents.

Mechanism of action

Unbound glucocorticoids cross cell membranes and bind with high affinity to specific cytoplasmic receptors, modifying transcription and protein synthesis. By this mechanism, glucocorticoids can inhibit leukocyte infiltration at the site of inflammation, interfere with mediators of inflammatory response, and suppress humoral immune responses. The antiinflammatory actions of corticosteroids are thought to involve phospholipase A2 inhibitory proteins, lipocortins, which control the biosynthesis of potent mediators of inflammation such as prostaglandins and leukotrienes.

Absorption

Oral bioavailability 80-99%

Volume of distribution

Not Available

Protein binding

78%

Metabolism

Hepatic

Route of elimination

Not Available

Half life

1-3 hours

Clearance

Not Available

Toxicity

LD₅₀=2000 mg/kg (orally in rat)

Affected organisms

Humans and other mammals

Pathways

Not Available

Pharmacoeconomics

Manufacturers

Pharmacia and upjohn co
Cadista pharmaceuticals inc
Duramed pharmaceuticals inc sub barr laboratories inc
Heather drug co inc
Par pharmaceutical inc
Sandoz inc
Vintage pharmaceuticals inc
Watson laboratories inc
Abbott laboratories hosp products div
Hemopharm usa corp
Hospira inc
Elkins sinn div ah robins co inc
Organon usa inc
Abraxis pharmaceutical products
App pharmaceuticals llc
Bedford laboratories
International medication systems ltd
Teva parenteral medicines inc

Packagers

Dosage forms

Form	Route	Strength
Powder	Intramuscular
Powder	Intravenous
Powder, for solution	Intravenous
Suspension	Intramuscular
Tablet	Oral

Prices

Unit description	Cost	Unit
Methylprednisolone powder	96.25 USD	g
Methylprednisolone ac powdr	40.09 USD	g
Methylprednisolone ss 1 gm vial	31.2 USD	vial
Solu-medrol 1 gm vial	24.43 USD	vial
Solu-medrol (pf) 500 mg vial	20.9 USD	vial
MethylPREDNISolone (Pak) 21 4 mg tablet Disp Pack	16.99 USD	disp
Methylprednisolone 500 mg vial	15.6 USD	vial
Solu-medrol 500 mg vial	12.9 USD	vial
Depo-medrol 80 mg/ml vial	11.67 USD	ml
Methylprednisolone 125 mg vial	10.0 USD	vial
Methylprednisolone 80 mg/ml vial	9.12 USD	ml
Depo-medrol 40 mg/ml vial	6.41 USD	ml
Solu-medrol (pf) 125 mg vial	5.83 USD	vial
Methylprednisolone 40 mg/ml vial	5.22 USD	ml
Medrol 32 mg tablet	5.13 USD	tablet
Methylprednisolone 32 mg tablet	4.62 USD	tablet
Depo-medrol 20 mg/ml vial	3.78 USD	ml
Methylprednisolone 16 mg tablet	3.17 USD	tablet
Methylprednisolone 40 mg vial	3.0 USD	vial
A-methapred 40 mg vial	2.36 USD	vial
Medrol 16 mg tablet	2.28 USD	tablet
Medrol 8 mg tablet	2.23 USD	tablet
Methylprednisolone 8 mg tablet	1.74 USD	tablet
Methylprednisolone 4 mg tablet	1.68 USD	tablet
Medrol 4 mg dosepak	1.59 USD	each
Medrol 4 mg tablet	0.99 USD	tablet
Medrol 2 mg tablet	0.84 USD	tablet

Patents

Not Available

Properties

State

solid

Melting point

232.5 oC

Experimental Properties

Property	Value	Source
water solubility	120 mg/L	PhysProp
logP	1.5	PhysProp
logS	-2.99 [ADME Research, USCD]	PhysProp

Predicted Properties

Property	Value	Source
water solubility	1.09e-01 g/l	ALOGPS
logP	2.06	ALOGPS
logP	1.56	ChemAxon Molconvert
logS	-3.54	ALOGPS
pKa	13.86	ChemAxon Molconvert
hydrogen acceptor count	5	ChemAxon Molconvert
hydrogen donor count	3	ChemAxon Molconvert
polar surface area	94.83	ChemAxon Molconvert
rotatable bond count	2	ChemAxon Molconvert
refractivity	103.04	ChemAxon Molconvert
polarizability	40.84	ChemAxon Molconvert

References

Synthesis Reference

Not Available

General Reference

Sloka JS, Stefanelli M: The mechanism of action of methylprednisolone in the treatment of multiple sclerosis. Mult Scler. 2005 Aug;11(4):425-32. Pubmed

External Links

Resource	Link
KEGG Drug	D00407
PubChem Compound	6741
PubChem Substance	46504885
ChemSpider	6485
ChEBI	6888
ChEMBL	6888
Therapeutic Targets Database	DAP001040
PharmGKB	PA450466
Drug Product Database	2245406
RxList	http://www.rxlist.com/cgi/generic/methprd.htm
Drugs.com	http://www.drugs.com/methylprednisolone.html
Wikipedia	http://en.wikipedia.org/wiki/Methylprednisolone

ATC Codes

D07AA01
D07AC14
D10AA02
H02AB04

AHFS Codes

68:04.00

PDB Entries

Not Available

FDA label

show (244 KB)

MSDS

show (72.6 KB)

Interactions

Drug Interactions

Not Available

Food Interactions

Not Available

Targets
1. Glucocorticoid receptor Pharmacological action: yes Actions: agonist Receptor for glucocorticoids (GC). Has a dual mode of action:as a transcription factor that binds to glucocorticoid response elements (GRE) and as a modulator of other transcription factors. Affects inflammatory responses, cellular proliferation and differentiation in target tissues. Could act as a coactivator for STAT5-dependent transcription upon growth hormone (GH) stimulation and could reveal an essential role of hepatic GR in the control of body growth Organism class: human UniProt ID: P04150 Gene: NR3C1 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: Owen HC, Miner JN, Ahmed SF, Farquharson C: The growth plate sparing effects of the selective glucocorticoid receptor modulator, AL-438. Mol Cell Endocrinol. 2007 Jan 29;264(1-2):164-70. Epub 2006 Dec 19. Pubmed Juruena MF, Cleare AJ, Papadopoulos AS, Poon L, Lightman S, Pariante CM: Different responses to dexamethasone and prednisolone in the same depressed patients. Psychopharmacology (Berl). 2006 Dec;189(2):225-35. Epub 2006 Oct 3. Pubmed Boivin MA, Ye D, Kennedy JC, Al-Sadi R, Shepela C, Ma TY: Mechanism of glucocorticoid regulation of the intestinal tight junction barrier. Am J Physiol Gastrointest Liver Physiol. 2007 Feb;292(2):G590-8. Epub 2006 Oct 26. Pubmed Quesnell RR, Han X, Schultz BD: Glucocorticoids stimulate ENaC upregulation in bovine mammary epithelium. Am J Physiol Cell Physiol. 2007 May;292(5):C1739-45. Epub 2007 Jan 24. Pubmed Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

Targets

1. Glucocorticoid receptor

Pharmacological action: yes
Actions: agonist

Receptor for glucocorticoids (GC). Has a dual mode of action:as a transcription factor that binds to glucocorticoid response elements (GRE) and as a modulator of other transcription factors. Affects inflammatory responses, cellular proliferation and differentiation in target tissues. Could act as a coactivator for STAT5-dependent transcription upon growth hormone (GH) stimulation and could reveal an essential role of hepatic GR in the control of body growth

Organism class: human
UniProt ID: P04150 Link_out

Gene: NR3C1 Link_out

Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

Owen HC, Miner JN, Ahmed SF, Farquharson C: The growth plate sparing effects of the selective glucocorticoid receptor modulator, AL-438. Mol Cell Endocrinol. 2007 Jan 29;264(1-2):164-70. Epub 2006 Dec 19. Pubmed
Juruena MF, Cleare AJ, Papadopoulos AS, Poon L, Lightman S, Pariante CM: Different responses to dexamethasone and prednisolone in the same depressed patients. Psychopharmacology (Berl). 2006 Dec;189(2):225-35. Epub 2006 Oct 3. Pubmed
Boivin MA, Ye D, Kennedy JC, Al-Sadi R, Shepela C, Ma TY: Mechanism of glucocorticoid regulation of the intestinal tight junction barrier. Am J Physiol Gastrointest Liver Physiol. 2007 Feb;292(2):G590-8. Epub 2006 Oct 26. Pubmed
Quesnell RR, Han X, Schultz BD: Glucocorticoids stimulate ENaC upregulation in bovine mammary epithelium. Am J Physiol Cell Physiol. 2007 May;292(5):C1739-45. Epub 2007 Jan 24. Pubmed
Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

Enzymes
1. Cytochrome P450 3A4 Actions: substrate, inhibitor 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 reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4- hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. The enzyme also hydroxylates etoposide UniProt ID: P08684 Gene: CYP3A4 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: 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

Enzymes

1. Cytochrome P450 3A4

Actions: substrate, inhibitor

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 reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4- hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. The enzyme also hydroxylates etoposide

UniProt ID: P08684 Link_out

Gene: CYP3A4
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

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

Transporters
1. Multidrug resistance protein 1 Actions: substrate Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells UniProt ID: P08183 Gene: ABCB1 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: Oka A, Oda M, Saitoh H, Nakayama A, Takada M, Aungst BJ: Secretory transport of methylprednisolone possibly mediated by P-glycoprotein in Caco-2 cells. Biol Pharm Bull. 2002 Mar;25(3):393-6. Pubmed Troutman MD, Thakker DR: Novel experimental parameters to quantify the modulation of absorptive and secretory transport of compounds by P-glycoprotein in cell culture models of intestinal epithelium. Pharm Res. 2003 Aug;20(8):1210-24. Pubmed Yates CR, Chang C, Kearbey JD, Yasuda K, Schuetz EG, Miller DD, Dalton JT, Swaan PW: Structural determinants of P-glycoprotein-mediated transport of glucocorticoids. Pharm Res. 2003 Nov;20(11):1794-803. Pubmed

Transporters

1. Multidrug resistance protein 1

Actions: substrate

Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells

UniProt ID: P08183 Link_out

Gene: ABCB1 Link_out

Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

Oka A, Oda M, Saitoh H, Nakayama A, Takada M, Aungst BJ: Secretory transport of methylprednisolone possibly mediated by P-glycoprotein in Caco-2 cells. Biol Pharm Bull. 2002 Mar;25(3):393-6. Pubmed
Troutman MD, Thakker DR: Novel experimental parameters to quantify the modulation of absorptive and secretory transport of compounds by P-glycoprotein in cell culture models of intestinal epithelium. Pharm Res. 2003 Aug;20(8):1210-24. Pubmed
Yates CR, Chang C, Kearbey JD, Yasuda K, Schuetz EG, Miller DD, Dalton JT, Swaan PW: Structural determinants of P-glycoprotein-mediated transport of glucocorticoids. Pharm Res. 2003 Nov;20(11):1794-803. Pubmed

Comments

Drug created on June 13, 2005 07:24 / Updated on April 19, 2011 15:07

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.