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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Associated Conditions
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.

TargetActionsOrganism
AProstaglandin E2 receptor EP2 subtype
agonist
Humans
UProstaglandin E2 receptor EP1 subtype
agonist
Humans
UProstaglandin E2 receptor EP3 subtype
agonist
Humans
UProstaglandin E2 receptor EP4 subtypeNot AvailableHumans
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.
DrugInteraction
AbciximabThe risk or severity of adverse effects can be increased when Limaprost is combined with Abciximab.
AceclofenacThe therapeutic efficacy of Limaprost can be decreased when used in combination with Aceclofenac.
AcemetacinThe therapeutic efficacy of Limaprost can be decreased when used in combination with Acemetacin.
AcenocoumarolThe risk or severity of adverse effects can be increased when Limaprost is combined with Acenocoumarol.
Acetylsalicylic acidLimaprost may increase the antiplatelet activities of Acetylsalicylic acid.
AlclofenacThe therapeutic efficacy of Limaprost can be decreased when used in combination with Alclofenac.
AlteplaseThe risk or severity of adverse effects can be increased when Limaprost is combined with Alteplase.
AminophenazoneThe therapeutic efficacy of Limaprost can be decreased when used in combination with Aminophenazone.
AnagrelideLimaprost may increase the antiplatelet activities of Anagrelide.
AncrodThe risk or severity of adverse effects can be increased when Limaprost is combined with Ancrod.
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Food Interactions
Not Available

Products

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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
  1. 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]
  2. 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]
  3. 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]
KEGG Drug
D02722
PubChem Compound
6438378
PubChem Substance
310265118
ChemSpider
4942859
ChEBI
135594
ChEMBL
CHEMBL2107456
ZINC
ZINC000004216741
FDA label
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Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4CompletedTreatmentNeurologic Claudication in Patients With Lumbar Spinal Stenosis1
3RecruitingTreatmentMyelopathy Cervical1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
Tablet5 mcg
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0248 mg/mLALOGPS
logP4.03ALOGPS
logP4.32ChemAxon
logS-4.2ALOGPS
pKa (Strongest Acidic)4.44ChemAxon
pKa (Strongest Basic)-1.5ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area94.83 Å2ChemAxon
Rotatable Bond Count13ChemAxon
Refractivity108.56 m3·mol-1ChemAxon
Polarizability45.22 Å3ChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET Features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Targets

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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
  1. 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