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Identification
Name Risedronate
Accession Number DB00884 (APRD00410, DB02782)
Type small molecule
Groups approved
Description

Risedronate is a bisphosphonate used to strengthen bone, treat or prevent osteoporosis, and treat Paget’s disease of bone.
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
NE-58095
Risedronate sodium
Risedronic acid
Salts Not Available
Brand names
Name Company
Actonel Warner Chilcott, Procter & Gamble
Actonel 150
Benet
Brand mixtures
Brand Name Ingredients
Actonal Plus Calcium (Warner Chilcott) risedronate sodium hemi-pentahydrate + calcium carbonate
Actonel with Calcium (Procter & Gamble) risedronate sodium + calcium carbonate
Categories
  • Antihypocalcemic Agents
  • Calcium Channel Blockers
  • Bisphosphonates
  • Antiresorptives
  • Bone Density Conservation Agents
CAS number 105462-24-6
Weight Average: 283.1123
Monoisotopic: 283.001074735
Chemical Formula C7H11NO7P2
InChI Key InChIKey=IIDJRNMFWXDHID-UHFFFAOYSA-N
InChI
InChI=1S/C7H11NO7P2/c9-7(16(10,11)12,17(13,14)15)4-6-2-1-3-8-5-6/h1-3,5,9H,4H2,(H2,10,11,12)(H2,13,14,15)
Plain Text
IUPAC Name
[1-hydroxy-1-phosphono-2-(pyridin-3-yl)ethyl]phosphonic acid
SMILES
OC(CC1=CN=CC=C1)(P(O)(O)=O)P(O)(O)=O
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Bisphosphonates
Substructures
  • Hydroxy Compounds
  • Carboxylic Acids and Derivatives
  • Phosphonic Acids and Derivatives
  • Pyridines and Derivatives
  • Heterocyclic compounds
  • Aromatic compounds
  • Phosphinic Acids and Derivatives
  • Bisphosphonates
Pharmacology
Indication For the treatment of Paget's disease of the bone (osteitis deformans), postmenopausal and glucocorticoid-induced osteoporosis
Pharmacodynamics Risedronate is a pyridinyl bisphosphonate that inhibits osteoclast-mediated bone resorption and modulates bone metabolism and is indicated for the treatment and prevention of osteoporosis in postmenopausal women.
Mechanism of action The action of risedronate on bone tissue is based partly on its affinity for hydroxyapatite, which is part of the mineral matrix of bone. Risedronate also targets farnesyl pyrophosphate (FPP) synthase. Nitrogen-containing bisphosphonates (such as pamidronate, alendronate, risedronate, ibandronate and zoledronate) appear to act as analogues of isoprenoid diphosphate lipids, thereby inhibiting FPP synthase, an enzyme in the mevalonate pathway. Inhibition of this enzyme in osteoclasts prevents the biosynthesis of isoprenoid lipids (FPP and GGPP) that are essential for the post-translational farnesylation and geranylgeranylation of small GTPase signalling proteins. This activity inhibits osteoclast activity and reduces bone resorption and turnover. In postmenopausal women, it reduces the elevated rate of bone turnover, leading to, on average, a net gain in bone mass.
Absorption Rapid absorption (~1 hr) after an oral dose, occurs throughout the upper gastrointestinal tract
Volume of distribution
  • 13.8 L/kg
Protein binding ~24%
Metabolism No evidence found for metabolization of risedronate in humans or mammals
Route of elimination Risedronate is excreted unchanged primarily via the kidney. Insignificant amounts (<0.1% of intravenous dose) of drug are excreted in the bile in rats.
Half life 1.5 hours
Clearance
  • 122 mL/min
  • 73 mL/min [osteopenic postmenopausal women]
Toxicity Side effects include abdominal pain, anxiety, back pain, belching, bladder irritation, bone disorders and pain, bronchitis, bursitis, cataracts, chest pain, colitis, constipation, depression, diarrhea, difficulty breathing, dizziness, dry eyes, eye infection, flu-like symptoms, gas, headache, high blood pressure, infection, insomnia, itching, joint disorders and pain, leg cramps, muscle pain, muscle weakness, nausea, neck pain, nerve pain, pain, pneumonia, rash, ringing in ears, sinus problems, sore throat, stomach bleeding, stuffy or runny nose, swelling, tendon problems, tumor, ulcers, urinary tract infection, vertigo, vision problems, and weakness.
Affected organisms
  • Humans and other mammals
Pathways
Pathway Name SMPDB ID
Smp00112 Risedronate Pathway SMP00112
Pharmacoeconomics
Manufacturers
  • Warner chilcott co llc
  • Teva pharmaceuticals usa
  • Procter & Gamble
Packagers
Dosage forms
Form Route Strength
Tablet, film coated Oral 150 mg
Tablet, film coated Oral 30 mg
Tablet, film coated Oral 35 mg
Tablet, film coated Oral 5 mg
Tablet, film coated Oral 75 mg
Prices
Unit description Cost Unit
Actonel 150 mg tablet 125.1 USD tablet
Actonel 4 35 mg tablet Disp Pack 119.43 USD disp
Actonel 75 mg tablet 54.83 USD tablet
Actonel 30 mg tablet 29.32 USD tablet
Actonel 35 mg tablet 28.75 USD tablet
Actonel 5 mg tablet 4.13 USD tablet
Actonel with calcium tablet 3.92 USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Country Patent Number Approved Expires (estimated)
United States 7192938 2003-11-06 2023-11-06
United States 6096342 1994-11-22 2011-11-22
Canada 2294595 2001-08-21 2018-07-17
Canada 2399976 2007-03-27 2021-02-01
Properties
State solid
Experimental Properties
Property Value Source
logP -3.6 Not Available
Predicted Properties
Property Value Source
water solubility 1.04e+01 g/l ALOGPS
logP -0.75 ALOGPS
logP -3.3 ChemAxon
logS -1.4 ALOGPS
pKa (strongest acidic) 0.68 ChemAxon
pKa (strongest basic) 4.91 ChemAxon
physiological charge -2 ChemAxon
hydrogen acceptor count 8 ChemAxon
hydrogen donor count 5 ChemAxon
polar surface area 148.18 ChemAxon
rotatable bond count 4 ChemAxon
refractivity 57.12 ChemAxon
polarizability 21.91 ChemAxon
References
Synthesis Reference Not Available
General Reference Not Available
External Links
Resource Link
KEGG Compound C08233 Link_out
PubChem Compound 5245 Link_out
PubChem Substance 46507526 Link_out
ChemSpider 5055 Link_out
BindingDB 12576 Link_out
Therapeutic Targets Database DAP000658 Link_out
PharmGKB PA451255 Link_out
HET RIS Link_out
Drug Product Database 2242518 Link_out
RxList http://www.rxlist.com/cgi/generic/risedronate.htm Link_out
Drugs.com http://www.drugs.com/cdi/risedronate-tablets.html Link_out
PDRhealth http://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/act1580.shtml Link_out
Wikipedia http://en.wikipedia.org/wiki/Risedronate Link_out
ATC Codes
  • M05BA07
AHFS Codes
  • 92:00.00
PDB Entries
FDA label show (1.52 MB)
MSDS show (57 KB)
Interactions
Drug Interactions
Drug Interaction
Calcium Formation of non-absorbable complexes
Calcium Acetate Calcium Salts may decrease the serum concentration of Bisphosphonate Derivatives such as risedronate. Avoid administration of oral calcium supplements within or 30 minutes after risedronate.
Calcium Chloride Calcium salts may decrease the serum concentration of bisphosphonate derivatives. Avoid administration of oral calcium supplements within 30 minutes after alendronate/risedronate.
Iron Dextran Formation of non-absorbable complexes
Magnesium Formation of non-absorbable complexes
Food Interactions Not Available
Targets

1. Farnesyl pyrophosphate synthetase

Pharmacological action: yes
Actions: inhibitor

Catalyzes the sequential condensation of isopentenyl pyrophosphate with the allylic pyrophosphates, dimethylallyl pyrophosphate, and then with the resultant geranylpyrophosphate to the ultimate product farnesyl pyrophosphate

Organism class: human
UniProt ID: P14324 Link_out
Gene: FDPS Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Bergstrom JD, Bostedor RG, Masarachia PJ, Reszka AA, Rodan G: Alendronate is a specific, nanomolar inhibitor of farnesyl diphosphate synthase. Arch Biochem Biophys. 2000 Jan 1;373(1):231-41. Pubmed
  2. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
  3. Coxon FP, Ebetino FH, Mules EH, Seabra MC, McKenna CE, Rogers MJ: Phosphonocarboxylate inhibitors of Rab geranylgeranyl transferase disrupt the prenylation and membrane localization of Rab proteins in osteoclasts in vitro and in vivo. Bone. 2005 Sep;37(3):349-58. Pubmed
  4. Dunford JE, Thompson K, Coxon FP, Luckman SP, Hahn FM, Poulter CD, Ebetino FH, Rogers MJ: Structure-activity relationships for inhibition of farnesyl diphosphate synthase in vitro and inhibition of bone resorption in vivo by nitrogen-containing bisphosphonates. J Pharmacol Exp Ther. 2001 Feb;296(2):235-42. Pubmed
  5. Ortiz-Gomez A, Jimenez C, Estevez AM, Carrero-Lerida J, Ruiz-Perez LM, Gonzalez-Pacanowska D: Farnesyl diphosphate synthase is a cytosolic enzyme in Leishmania major promastigotes and its overexpression confers resistance to risedronate. Eukaryot Cell. 2006 Jul;5(7):1057-64. Pubmed
  6. Russell RG, Xia Z, Dunford JE, Oppermann U, Kwaasi A, Hulley PA, Kavanagh KL, Triffitt JT, Lundy MW, Phipps RJ, Barnett BL, Coxon FP, Rogers MJ, Watts NB, Ebetino FH: Bisphosphonates: an update on mechanisms of action and how these relate to clinical efficacy. Ann N Y Acad Sci. 2007 Nov;1117:209-57. Pubmed

2. Hydroxyapatite

Pharmacological action: yes
Actions: antagonist

References:
  1. Jahnke W, Henry C: An in vitro assay to measure targeted drug delivery to bone mineral. ChemMedChem. 2010 May 3;5(5):770-6. Pubmed
  2. Nancollas GH, Tang R, Phipps RJ, Henneman Z, Gulde S, Wu W, Mangood A, Russell RG, Ebetino FH: Novel insights into actions of bisphosphonates on bone: differences in interactions with hydroxyapatite. Bone. 2006 May;38(5):617-27. Epub 2005 Jul 20. Pubmed
Enzymes

1. Prostaglandin G/H synthase 2

Actions: inducer

May have a role as a major mediator of inflammation and/or a role for prostanoid signaling in activity-dependent plasticity

UniProt ID: P35354 Link_out
Gene: PTGS2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Valenti MT, Giannini S, Donatelli L, Zanatta M, Bertoldo F, Sella S, Vilei MT, Ossi E, Realdi G, Lo Cascio V, Dalle Carbonare L: The effect of risedronate on osteogenic lineage is mediated by cyclooxygenase-2 gene upregulation. Arthritis Res Ther. 2010;12(4):R163. Epub 2010 Aug 25. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on February 08, 2013 16:19