Limaprost
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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- 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
- Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates.Improve decision support & research outcomes with our structured adverse effects data.
- 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 therapeutic efficacy of Limaprost can be decreased when used in combination with Aceclofenac. Acemetacin The therapeutic efficacy of Limaprost can be decreased when used in combination with Acemetacin. Acenocoumarol The risk or severity of adverse effects can be increased when Limaprost is combined with Acenocoumarol. Acetylsalicylic acid Limaprost may increase the antiplatelet activities of Acetylsalicylic acid. Alclofenac The therapeutic efficacy of Limaprost can be decreased when used in combination with Alclofenac. Alteplase The risk or severity of adverse effects can be increased when Limaprost is combined with Alteplase. Aminophenazone The therapeutic efficacy of Limaprost can be decreased when used in combination with Aminophenazone. Anagrelide Limaprost may increase the antiplatelet activities of Anagrelide. Ancrod The risk or severity of adverse effects can be increased when Limaprost is combined with Ancrod. Identify potential medication risksEasily compare up to 40 drugs with our drug interaction checker.Get severity rating, description, and management advice.Learn more - 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
- 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
Phase Status Purpose Conditions Count 4 Completed Treatment Neurologic Claudication in Patients With Lumbar Spinal Stenosis 1 3 Completed Treatment Myelopathy Cervical 1
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 Not Available Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS Not Available
Targets

- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Agonist
- General Function
- Prostaglandin e receptor activity
- Specific 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 ...
- 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
- Prostaglandin e receptor activity
- Specific 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 importa...
- 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
- Rna polymerase ii transcription factor activity, ligand-activated sequence-specific dna binding
- Specific Function
- Receptor for prostaglandin E2 (PGE2); the EP3 receptor may be involved in inhibition of gastric acid secretion, modulation of neurotransmitter release in central and peripheral neurons, inhibition ...
- 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
- Prostaglandin e receptor activity
- Specific 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...
- 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