Identification
- Generic Name
- Flupirtine
- DrugBank Accession Number
- DB06623
- Background
Flupirtine is a pyridine derivative that is in clinical use as a nonopioid analgesic. It was approved for the treatment of pain in 1984 in Europe. It is not approved for use in the U.S. or Canada, but is currently in phase II trials for the treatment of fibromyalgia.
- Type
- Small Molecule
- Groups
- Investigational
- Structure
Structure for Flupirtine (DB06623)
- Weight
- Average: 304.3195
Monoisotopic: 304.133554013 - Chemical Formula
- C15H17FN4O2
- Synonyms
- Flupirtine
- Flupirtino
- Flupirtinum
Pharmacology
- Indication
Investigated for use/treatment in fibromyalgia.
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Avoid life-threatening adverse drug eventsImprove clinical decision support with information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events & improve clinical decision support.- Pharmacodynamics
Not Available
- Mechanism of action
Flupirtine upregulates Bcl-2, increases glutathione levels, activates an inwardly rectifying potassium channel, and delays loss of intermitochondrial membrane calcium retention capacity. Flupirtine acts like a NMDA receptor antagonists, but does not bind to the receptor. One study concluded that the discriminative effects of flupirtine are neither of opioid nor of alpha-1 adrenergic type, but are primarily mediated through alpha-2 adrenergic mechanisms [PMID: 2901483].
Target Actions Organism UAlpha-2A adrenergic receptor Not Available Humans - Absorption
Bioavailability: 90% (oral), 70% (rectal)
- Volume of distribution
Not Available
- Protein binding
Not Available
- Metabolism
Hepatic to 2-amino-3-acetylamino-6-(para-fluorobenzylamino) pyridine (which has 20-30% the analgesic potential of its parent compound) and Para-fluorohippuric acid.
- Route of elimination
72% of flupirtine and its metabolites appear in urine and 18% appear in faeces.
- Half-life
6.5 hrs (average), 11.2-16.8 hrs (average 14 hrs) (elderly), 8.7-10.9 hrs (average 9.8 hrs) (in those with moderate-level renal impairment).
- Clearance
Not Available
- Adverse Effects
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Oral, mouse: LD50 = 300 mg/kg; Oral, rabbit: LD50 = 3200 mg/kg; Oral, rat: LD50 = 980 mg/kg.
- 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 softwareAbacavir Abacavir may decrease the excretion rate of Flupirtine which could result in a higher serum level. Aceclofenac Aceclofenac may decrease the excretion rate of Flupirtine which could result in a higher serum level. Acemetacin Acemetacin may decrease the excretion rate of Flupirtine which could result in a higher serum level. Acetaminophen Acetaminophen may decrease the excretion rate of Flupirtine which could result in a higher serum level. Acetazolamide Acetazolamide may increase the excretion rate of Flupirtine which could result in a lower serum level and potentially a reduction in efficacy. Acetylsalicylic acid Acetylsalicylic acid may decrease the excretion rate of Flupirtine which could result in a higher serum level. Aclidinium Flupirtine may decrease the excretion rate of Aclidinium which could result in a higher serum level. Acrivastine Flupirtine may decrease the excretion rate of Acrivastine which could result in a higher serum level. Acyclovir Acyclovir may decrease the excretion rate of Flupirtine which could result in a higher serum level. Adefovir dipivoxil Adefovir dipivoxil may decrease the excretion rate of Flupirtine which could result in a higher serum level. 
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- 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.- Product Ingredients
Ingredient UNII CAS InChI Key Flupirtine gluconate D7NP6CR89M 815586-85-7 KTUKTXYTLNEYHO-IFWQJVLJSA-N Flupirtine maleate 0VCI53PK4A 75507-68-5 DPYIXBFZUMCMJM-BTJKTKAUSA-N - International/Other Brands
- Awegal / Effirma / Efiret / Katadolon / Metanor / Trancolong
Categories
- ATC Codes
- N02BG07 — Flupirtine
- Drug Categories
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as 2-benzylaminopyridines. These are aromatic compounds containing pyridine ring substituted at the 2-position by a benzylamine group.
- Kingdom
- Organic compounds
- Super Class
- Benzenoids
- Class
- Benzene and substituted derivatives
- Sub Class
- Benzylamines
- Direct Parent
- 2-benzylaminopyridines
- Alternative Parents
- Secondary alkylarylamines / Fluorobenzenes / Aminopyridines and derivatives / Imidolactams / Aryl fluorides / Heteroaromatic compounds / Carbamate esters / Organic carbonic acids and derivatives / Azacyclic compounds / Primary amines show 5 more
- Substituents
- 2-benzylaminopyridine / Amine / Aminopyridine / Aromatic heteromonocyclic compound / Aryl fluoride / Aryl halide / Azacycle / Carbamic acid ester / Carbonic acid derivative / Carbonyl group show 18 more
- Molecular Framework
- Aromatic heteromonocyclic compounds
- External Descriptors
- Not Available
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- MOH3ET196H
- CAS number
- 56995-20-1
- InChI Key
- JUUFBMODXQKSTD-UHFFFAOYSA-N
- InChI
- InChI=1S/C15H17FN4O2/c1-2-22-15(21)19-12-7-8-13(20-14(12)17)18-9-10-3-5-11(16)6-4-10/h3-8H,2,9H2,1H3,(H,19,21)(H3,17,18,20)
- IUPAC Name
- ethyl N-(2-amino-6-{[(4-fluorophenyl)methyl]amino}pyridin-3-yl)carbamate
- SMILES
- CCOC(=O)NC1=C(N)N=C(NCC2=CC=C(F)C=C2)C=C1
References
- General References
- Muller WE, Laplanche JL, Ushijima H, Schroder HC: Novel approaches in diagnosis and therapy of Creutzfeldt-Jakob disease. Mech Ageing Dev. 2000 Jul 31;116(2-3):193-218. [Article]
- Dhar S, Bitting RL, Rylova SN, Jansen PJ, Lockhart E, Koeberl DD, Amalfitano A, Boustany RM: Flupirtine blocks apoptosis in batten patient lymphoblasts and in human postmitotic CLN3- and CLN2-deficient neurons. Ann Neurol. 2002 Apr;51(4):448-66. [Article]
- Swedberg MD, Shannon HE, Nickel B, Goldberg SR: Pharmacological mechanisms of action of flupirtine: a novel, centrally acting, nonopioid analgesic evaluated by its discriminative effects in the rat. J Pharmacol Exp Ther. 1988 Sep;246(3):1067-74. [Article]
- Abrams SM, Baker LR, Crome P, White AS, Johnston A, Ankier SI, Warrington SJ, Turner P, Niebch G: Pharmacokinetics of flupirtine in elderly volunteers and in patients with moderate renal impairment. Postgrad Med J. 1988 May;64(751):361-3. [Article]
- Narang PK, Tourville JF, Chatterji DC, Gallelli JF: Quantitation of flupirtine and its active acetylated metabolite by reversed-phase high-performance liquid chromatography using fluorometric detection. J Chromatogr. 1984 Jan 13;305(1):135-43. [Article]
- External Links
- KEGG Drug
- D07978
- PubChem Compound
- 53276
- PubChem Substance
- 175427080
- ChemSpider
- 48119
- BindingDB
- 81199
- 25193
- ChEBI
- 94646
- ChEMBL
- CHEMBL255044
- ZINC
- ZINC000000001473
- PharmGKB
- PA166152829
- Wikipedia
- Flupirtine
- MSDS
- Download (568 KB)
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 2 Terminated Treatment Relapsing Remitting Multiple Sclerosis (RRMS) 1 1 Completed Not Available Axonal Change, Neuronal / Pain 1 1 Completed Basic Science Flupirtine / Pain / Pharmacokinetics 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Capsule Suppository - Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 115.5 °C PhysProp - Predicted Properties
Property Value Source Water Solubility 0.0732 mg/mL ALOGPS logP 2.61 ALOGPS logP 2.67 Chemaxon logS -3.6 ALOGPS pKa (Strongest Acidic) 12.9 Chemaxon pKa (Strongest Basic) 7.5 Chemaxon Physiological Charge 1 Chemaxon Hydrogen Acceptor Count 5 Chemaxon Hydrogen Donor Count 3 Chemaxon Polar Surface Area 89.27 Å2 Chemaxon Rotatable Bond Count 6 Chemaxon Refractivity 85.49 m3·mol-1 Chemaxon Polarizability 31.37 Å3 Chemaxon Number of Rings 2 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
Property Value Probability Human Intestinal Absorption + 0.9873 Blood Brain Barrier + 0.9373 Caco-2 permeable - 0.5757 P-glycoprotein substrate Substrate 0.5425 P-glycoprotein inhibitor I Non-inhibitor 0.8064 P-glycoprotein inhibitor II Non-inhibitor 0.959 Renal organic cation transporter Non-inhibitor 0.8922 CYP450 2C9 substrate Non-substrate 0.8747 CYP450 2D6 substrate Non-substrate 0.8227 CYP450 3A4 substrate Non-substrate 0.6669 CYP450 1A2 substrate Inhibitor 0.7646 CYP450 2C9 inhibitor Non-inhibitor 0.7681 CYP450 2D6 inhibitor Inhibitor 0.8931 CYP450 2C19 inhibitor Non-inhibitor 0.5559 CYP450 3A4 inhibitor Inhibitor 0.7559 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.5155 Ames test Non AMES toxic 0.6798 Carcinogenicity Non-carcinogens 0.8404 Biodegradation Not ready biodegradable 1.0 Rat acute toxicity 2.5191 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.9762 hERG inhibition (predictor II) Non-inhibitor 0.5543
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
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- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Thioesterase binding
- Specific Function
- Alpha-2 adrenergic receptors mediate the catecholamine-induced inhibition of adenylate cyclase through the action of G proteins. The rank order of potency for agonists of this receptor is oxymetazo...
- Gene Name
- ADRA2A
- Uniprot ID
- P08913
- Uniprot Name
- Alpha-2A adrenergic receptor
- Molecular Weight
- 48956.275 Da
References
- Swedberg MD, Shannon HE, Nickel B, Goldberg SR: Pharmacological mechanisms of action of flupirtine: a novel, centrally acting, nonopioid analgesic evaluated by its discriminative effects in the rat. J Pharmacol Exp Ther. 1988 Sep;246(3):1067-74. [Article]
Drug created at March 19, 2008 16:41 / Updated at March 03, 2023 17:45