Identification
NameFlupirtine
Accession NumberDB06623
TypeSmall Molecule
GroupsApproved, Investigational
Description

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.

Structure
Thumb
Synonyms
Flupirtine
External IDs Not Available
Product Ingredients
IngredientUNIICASInChI KeyDetails
Flupirtine gluconateD7NP6CR89M 815586-85-7KTUKTXYTLNEYHO-IFWQJVLJSA-NDetails
Flupirtine maleate0VCI53PK4A 75507-68-5DPYIXBFZUMCMJM-BTJKTKAUSA-NDetails
Approved Prescription ProductsNot Available
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
AwegalNot Available
EffirmaNot Available
EfiretNot Available
KatadolonNot Available
MetanorNot Available
TrancolongNot Available
Brand mixturesNot Available
Categories
UNIIMOH3ET196H
CAS number56995-20-1
WeightAverage: 304.3195
Monoisotopic: 304.133554013
Chemical FormulaC15H17FN4O2
InChI KeyJUUFBMODXQKSTD-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
Pharmacology
Indication

Investigated for use/treatment in fibromyalgia.

Structured Indications Not Available
PharmacodynamicsNot 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].

TargetKindPharmacological actionActionsOrganismUniProt ID
Alpha-2A adrenergic receptorProteinunknownNot AvailableHumanP08913 details
Related Articles
Absorption

Bioavailability: 90% (oral), 70% (rectal)

Volume of distributionNot Available
Protein bindingNot 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).

ClearanceNot Available
Toxicity

Oral, mouse: LD50 = 300 mg/kg; Oral, rabbit: LD50 = 3200 mg/kg; Oral, rat: LD50 = 980 mg/kg.

Affected organisms
  • Humans and other mammals
PathwaysNot Available
Pharmacogenomic Effects/ADRs Not Available
Interactions
Drug Interactions Not Available
Food InteractionsNot Available
References
Synthesis ReferenceNot Available
General References
  1. 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. [PubMed:10996019 ]
  2. 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. [PubMed:11921051 ]
  3. 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. [PubMed:2901483 ]
  4. 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. [PubMed:3200777 ]
  5. 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. [PubMed:6707137 ]
External Links
ATC CodesN02BG07 — Flupirtine
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSDownload (568 KB)
Clinical Trials
Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedNot AvailableAxonal Change, Neuronal / Pain1
1CompletedBasic ScienceFlupirtine / Pain / Pharmacokinetics1
2TerminatedTreatmentRelapsing Remitting Multiple Sclerosis (RRMS)1
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage formsNot Available
PricesNot Available
PatentsNot Available
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point (°C)115.5 °CPhysProp
Predicted Properties
PropertyValueSource
Water Solubility0.0732 mg/mLALOGPS
logP2.61ALOGPS
logP2.67ChemAxon
logS-3.6ALOGPS
pKa (Strongest Acidic)12.9ChemAxon
pKa (Strongest Basic)7.5ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area89.27 Å2ChemAxon
Rotatable Bond Count6ChemAxon
Refractivity85.49 m3·mol-1ChemAxon
Polarizability31.37 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9873
Blood Brain Barrier+0.9373
Caco-2 permeable-0.5757
P-glycoprotein substrateSubstrate0.5425
P-glycoprotein inhibitor INon-inhibitor0.8064
P-glycoprotein inhibitor IINon-inhibitor0.959
Renal organic cation transporterNon-inhibitor0.8922
CYP450 2C9 substrateNon-substrate0.8747
CYP450 2D6 substrateNon-substrate0.8227
CYP450 3A4 substrateNon-substrate0.6669
CYP450 1A2 substrateInhibitor0.7646
CYP450 2C9 inhibitorNon-inhibitor0.7681
CYP450 2D6 inhibitorInhibitor0.8931
CYP450 2C19 inhibitorNon-inhibitor0.5559
CYP450 3A4 inhibitorInhibitor0.7559
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.5155
Ames testNon AMES toxic0.6798
CarcinogenicityNon-carcinogens0.8404
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.5191 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9762
hERG inhibition (predictor II)Non-inhibitor0.5543
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
Taxonomy
DescriptionThis 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.
KingdomOrganic compounds
Super ClassBenzenoids
ClassBenzene and substituted derivatives
Sub ClassBenzylamines
Direct Parent2-benzylaminopyridines
Alternative ParentsSecondary alkylarylamines / Fluorobenzenes / Aminopyridines and derivatives / Imidolactams / Aryl fluorides / Heteroaromatic compounds / Carbamate esters / Organic carbonic acids and derivatives / Azacyclic compounds / Primary amines
Substituents2-benzylaminopyridine / Aminopyridine / Fluorobenzene / Halobenzene / Secondary aliphatic/aromatic amine / Aryl fluoride / Aryl halide / Pyridine / Imidolactam / Heteroaromatic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External DescriptorsNot Available

Targets

Kind
Protein
Organism
Human
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 oxymetazoline > clonidine > epinephrine > norepinephrine > phenylephrine > dopamine > p-synephrine > p-tyramine > serotonin = p-octopamine. For antagonists, the rank order is yohimbine > phentolamine = mianser...
Gene Name:
ADRA2A
Uniprot ID:
P08913
Uniprot Name:
Alpha-2A adrenergic receptor
Molecular Weight:
48956.275 Da
References
  1. 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. [PubMed:2901483 ]
Drug created on March 19, 2008 10:41 / Updated on June 11, 2017 21:01