Limaprost
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Identification
- Summary
Limaprost is an oral prostaglandin E1 analogue used to improve symptoms associated with thromboangiitis obliterans, acquired lumbar spinal canal stenosis, and other ischemic conditions.
- Generic Name
- Limaprost
- DrugBank Accession Number
- DB09211
- Background
Limaprost (as Limaprost alfadex; CAS number 88852-12-4) is an oral prostaglandin E1 analog. Prostaglandins act on a variety of cells such as vascular smooth muscle cells causing constriction or dilation, on platelets causing aggregation or disaggregation and on spinal neurons causing pain. Prostaglandins have a wide variety of actions, including, but not limited to muscular constriction and mediation of inflammation. Limaprost alfadex has been shown to improve peripheral circulatory failure with a vasodilator action and an antithrombotic effect. It also improves poor blood flow in the nerve tissue in cervical spondylosis and normalizes nerve function. Limaprost alfadex was discovered from collaborative research between Ono Pharmaceutical (Ono) and Dainippon Sumitomo Pharma (DSP). It was approved for the treatment of ischemic symptoms such as skin ulcer, pain and coldness accompanying thromboangiitis obliterans in 1988; and for the treatment of subjective symptoms such as pain and numbness in the lower leg and walking disability associated with acquired lumbar spinal canal stenosis as an additional indication in 2001. The drug has been sold under the trade name of Opalmon® Tablets by Ono and Prorenal® Tablets by DSP. In 2011, Ono and DSP initiated Phase II clinical trials in Japan for the treatment of carpal tunnel syndrome. In 2013, these trials were discontinued because the study failed to demonstrate efficacy. Ono and DSP also discontinued the development of limaprost alfadex for the additional indication of cervical spondylosis in 2008 due to the failure to demonstrate the anticipated efficacy in a Phase II study in patients with the disease. However, it was verified by Seoul National University Hospital in November of 2014 that the study on the efficacy of oral limaprost alfadex after surgery for cervical myelopathy was still ongoing.
- Type
- Small Molecule
- Groups
- Investigational
- Structure
- Weight
- Average: 380.525
Monoisotopic: 380.256274259 - Chemical Formula
- C22H36O5
- Synonyms
- Limaprost
- Limaprost alfadex
Pharmacology
- Indication
Limaprost is used for the improvement of various ischemic symptoms such as ulcer, pain and feeling of coldness associated with thromboangiitis obliterans as well as improvement of subjective symptoms (pain and numbness of lower legs) and gait ability associated with acquired lumbar spinal canal stenosis (in patients with bilateral intermittent claudication showing normal SLR test result).
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Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Treatment of Ischemic ulcers •••••••••••• •••••• Treatment of Pain caused by ischaemia •••••••••••• •••••• Symptomatic treatment of Thromboangiitis obliterans •••••••••••• •••••• - Contraindications & Blackbox Warnings
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- Pharmacodynamics
Limaprost produces vasodilation to improve blood flow to the extremities and increase cutaneous temperature Label.
- Mechanism of action
As a prostglandin E1 analog, limaprost acts as an agonist at prostraglandin E2 receptors. It likely stimulates the adenylate cyclase coupled E2 subtype of these receptors to produce smooth muscle relaxation 3.
Target Actions Organism AProstaglandin E2 receptor EP2 subtype agonistHumans UProstaglandin E2 receptor EP1 subtype agonistHumans UProstaglandin E2 receptor EP3 subtype agonistHumans UProstaglandin E2 receptor EP4 subtype Not Available Humans - Absorption
Limaprost reaches peak plasma concentration in about 30 minutes 2.
- Volume of distribution
Not Available
- Protein binding
Not Available
- Metabolism
- Not Available
- Route of elimination
Not Available
- Half-life
The mean half life of elimination is 1.64 hours 2.
- Clearance
Mean total clearance is 1.77 liters per hour 2.
- Adverse Effects
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- Toxicity
The most common adverse effects seen with limaprost are diarrhea, nausea/vomiting, flushing, abdominal discomfort, and headache Label.
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- 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.
Drug Interaction Integrate drug-drug
interactions in your softwareAbciximab The risk or severity of adverse effects can be increased when Limaprost is combined with Abciximab. Aceclofenac The risk or severity of bleeding and hemorrhage can be increased when Aceclofenac is combined with Limaprost. Acemetacin The risk or severity of bleeding and hemorrhage can be increased when Limaprost is combined with Acemetacin. Acenocoumarol The risk or severity of adverse effects can be increased when Limaprost is combined with Acenocoumarol. Acetylsalicylic acid Acetylsalicylic acid may increase the anticoagulant activities of Limaprost. - Food Interactions
- Not Available
Products
- Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.
- International/Other Brands
- Opalmon (Ono) / Prorenal (DSP)
Categories
- ATC Codes
- B01AC28 — Limaprost
- Drug Categories
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as long-chain fatty acids. These are fatty acids with an aliphatic tail that contains between 13 and 21 carbon atoms.
- Kingdom
- Organic compounds
- Super Class
- Lipids and lipid-like molecules
- Class
- Fatty Acyls
- Sub Class
- Fatty acids and conjugates
- Direct Parent
- Long-chain fatty acids
- Alternative Parents
- Hydroxy fatty acids / Branched fatty acids / Unsaturated fatty acids / Cyclopentanols / Cyclic ketones / Cyclic alcohols and derivatives / Monocarboxylic acids and derivatives / Carboxylic acids / Organic oxides / Hydrocarbon derivatives
- Substituents
- Alcohol / Aliphatic homomonocyclic compound / Branched fatty acid / Carbonyl group / Carboxylic acid / Carboxylic acid derivative / Cyclic alcohol / Cyclic ketone / Cyclopentanol / Hydrocarbon derivative
- Molecular Framework
- Aliphatic homomonocyclic compounds
- External Descriptors
- Not Available
- Affected organisms
- Not Available
Chemical Identifiers
- UNII
- L02U804092
- CAS number
- 74397-12-9
- InChI Key
- OJZYRQPMEIEQFC-UAWLTFRCSA-N
- InChI
- InChI=1S/C22H36O5/c1-3-4-9-16(2)14-17(23)12-13-19-18(20(24)15-21(19)25)10-7-5-6-8-11-22(26)27/h8,11-13,16-19,21,23,25H,3-7,9-10,14-15H2,1-2H3,(H,26,27)/b11-8+,13-12+/t16-,17+,18+,19+,21+/m0/s1
- IUPAC Name
- (2E)-7-[(1R,2R,3R)-3-hydroxy-2-[(1E,3S,5S)-3-hydroxy-5-methylnon-1-en-1-yl]-5-oxocyclopentyl]hept-2-enoic acid
- SMILES
- CCCC[C@H](C)C[C@H](O)\C=C\[C@H]1[C@H](O)CC(=O)[C@@H]1CCCC\C=C\C(O)=O
References
- General References
- Zhao HP, Xiang BR: Discontinued cardiovascular drugs in 2013 and 2014. Expert Opin Investig Drugs. 2015;24(8):1083-92. doi: 10.1517/13543784.2015.1051619. [Article]
- Park YS, Park JH, Kim SH, Lee MH, Lee YS, Yang SC, Kang JS: Pharmacokinetic characteristics of a vasodilatory and antiplatelet agent, limaprost alfadex, in the healthy Korean volunteers. Clin Appl Thromb Hemost. 2010 Jun;16(3):326-33. doi: 10.1177/1076029609334125. Epub 2009 Oct 13. [Article]
- Ruiz Rubio JL, Hernandez M, Rivera de los Arcos L, Martinez AC, Garcia-Sacristan A, Prieto D: Mechanisms of prostaglandin E1-induced relaxation in penile resistance arteries. J Urol. 2004 Feb;171(2 Pt 1):968-73. [Article]
- External Links
- KEGG Drug
- D02722
- PubChem Compound
- 6438378
- PubChem Substance
- 310265118
- ChemSpider
- 4942859
- ChEBI
- 135594
- ChEMBL
- CHEMBL2107456
- ZINC
- ZINC000004216741
- FDA label
- Download (57.7 KB)
Clinical Trials
- Clinical Trials
Clinical Trial & Rare Diseases Add-on Data Package
Explore 4,000+ rare diseases, orphan drugs & condition pairs, clinical trial why stopped data, & more. Preview package Phase Status Purpose Conditions Count Start Date Why Stopped 100+ additional columns Unlock 175K+ rows when you subscribe.View sample data4 Completed Treatment Neurologic Claudication in Patients With Lumbar Spinal Stenosis 1 somestatus stop reason just information to hide 3 Completed Treatment Myelopathy Cervical 1 somestatus stop reason just information to hide
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Tablet 5 mcg - Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
- Not Available
- Predicted Properties
Property Value Source Water Solubility 0.0248 mg/mL ALOGPS logP 4.03 ALOGPS logP 4.32 Chemaxon logS -4.2 ALOGPS pKa (Strongest Acidic) 4.44 Chemaxon pKa (Strongest Basic) -1.5 Chemaxon Physiological Charge -1 Chemaxon Hydrogen Acceptor Count 5 Chemaxon Hydrogen Donor Count 3 Chemaxon Polar Surface Area 94.83 Å2 Chemaxon Rotatable Bond Count 13 Chemaxon Refractivity 108.56 m3·mol-1 Chemaxon Polarizability 45.22 Å3 Chemaxon Number of Rings 1 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS splash10-0002-0009000000-1c96dfaa3799313ce141 Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS splash10-03dl-0009000000-9621cb72bca32e29d9c9 Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS splash10-0002-1469000000-1a731a9bed8b5a7a0ffc Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS splash10-00kf-0019000000-d2e03f07c3243b98f9ea Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS splash10-0540-4459000000-d277f63ad26e6bd73b88 Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS splash10-015a-7900000000-6b27f8b73e1371df6574 Predicted 1H NMR Spectrum 1D NMR Not Applicable Predicted 13C NMR Spectrum 1D NMR Not Applicable - Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 198.13887 predictedDeepCCS 1.0 (2019) [M+H]+ 200.53445 predictedDeepCCS 1.0 (2019) [M+Na]+ 206.44696 predictedDeepCCS 1.0 (2019)
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Agonist
- General Function
- Receptor for prostaglandin E2 (PGE2). The activity of this receptor is mediated by G(s) proteins that stimulate adenylate cyclase. The subsequent raise in intracellular cAMP is responsible for the relaxing effect of this receptor on smooth muscle
- Specific Function
- prostaglandin E receptor activity
- Gene Name
- PTGER2
- Uniprot ID
- P43116
- Uniprot Name
- Prostaglandin E2 receptor EP2 subtype
- Molecular Weight
- 39759.945 Da
References
- Ruiz Rubio JL, Hernandez M, Rivera de los Arcos L, Martinez AC, Garcia-Sacristan A, Prieto D: Mechanisms of prostaglandin E1-induced relaxation in penile resistance arteries. J Urol. 2004 Feb;171(2 Pt 1):968-73. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Agonist
- General Function
- Receptor for prostaglandin E2 (PGE2). The activity of this receptor is mediated by G(q) proteins which activate a phosphatidylinositol-calcium second messenger system. May play a role as an important modulator of renal function. Implicated the smooth muscle contractile response to PGE2 in various tissues
- Specific Function
- D1 dopamine receptor binding
- Gene Name
- PTGER1
- Uniprot ID
- P34995
- Uniprot Name
- Prostaglandin E2 receptor EP1 subtype
- Molecular Weight
- 41800.655 Da
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Agonist
- General Function
- Receptor for prostaglandin E2 (PGE2) (PubMed:7883006, PubMed:7981210, PubMed:8117308, PubMed:8135729, PubMed:8307176). The activity of this receptor can couple to both the inhibition of adenylate cyclase mediated by G(i) proteins, and to an elevation of intracellular calcium (PubMed:7883006, PubMed:7981210, PubMed:8117308, PubMed:8135729). Required for normal development of fever in response to pyrinogens, including IL1B, prostaglandin E2 and bacterial lipopolysaccharide (LPS). Required for normal potentiation of platelet aggregation by prostaglandin E2, and thus plays a role in the regulation of blood coagulation. Required for increased HCO3(-) secretion in the duodenum in response to mucosal acidification, and thereby contributes to the protection of the mucosa against acid-induced ulceration. Not required for normal kidney function, normal urine volume and osmolality (By similarity)
- Specific Function
- prostaglandin E receptor activity
- Gene Name
- PTGER3
- Uniprot ID
- P43115
- Uniprot Name
- Prostaglandin E2 receptor EP3 subtype
- Molecular Weight
- 43309.335 Da
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Receptor for prostaglandin E2 (PGE2). The activity of this receptor is mediated by G(s) proteins that stimulate adenylate cyclase. Has a relaxing effect on smooth muscle. May play an important role in regulating renal hemodynamics, intestinal epithelial transport, adrenal aldosterone secretion, and uterine function
- Specific Function
- prostaglandin E receptor activity
- Gene Name
- PTGER4
- Uniprot ID
- P35408
- Uniprot Name
- Prostaglandin E2 receptor EP4 subtype
- Molecular Weight
- 53118.845 Da
Drug created at October 20, 2015 20:32 / Updated at May 07, 2021 21:06