U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ACHIRAL
Molecular Formula C15H17FN4O2
Molecular Weight 304.3195
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of FLUPIRTINE

SMILES

CCOC(=O)NC1=CC=C(NCC2=CC=C(F)C=C2)N=C1N

InChI

InChIKey=JUUFBMODXQKSTD-UHFFFAOYSA-N
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)

HIDE SMILES / InChI
Flupirtine is a triaminopyridine derivative having a chemical structure - 2-amino-3-ethoxy-carbonylamino-6-4-fluoro-benzylamino-pyridine. The basic molecule used for synthesis of flupirtine was 2, 6-dichoro 3-nitropyridine. It was first synthesized in 1980s in Germany and was marketed by Degussa Pharma. Flupirtine is a centrally acting, non-opioid analgesic that is available in a number of European countries for the treatment of a variety of pain states. The therapeutic benefits seen with flupirtine relate to its unique pharmacological properties. Flupirtine displays indirect NDMA receptor antagonism via activation of potassium channels and is the first representative of a pharmacological class denoted the 'selective neuronal potassium channel openers'. The generation of the M-current is facilitated by flupirtine via the opening of neuronal Kv7 potassium channels. The opening of these channels inhibits exaggerated neuronal action potential generation and controls neuronal excitability. Neuronal hyperexcitability is a physiological component of many pain states such as chronic pain, migraine and neurogenic pain.

Approval Year

PubMed

PubMed

TitleDatePubMed
Pharmacokinetics of flupirtine in elderly volunteers and in patients with moderate renal impairment.
1988 May
Antiparkinsonian and other motor effects of flupirtine alone and in combination with dopaminergic drugs.
1997 May 26
Melatonin counteracts ischemia-induced apoptosis in human retinal pigment epithelial cells.
1998 Nov
Treatment of spasticity.
2002 Jun
Analgesic efficacy of flupirtine in primary care of patients with osteoporosis related pain. A multivariate analysis.
2003
Attenuation of methamphetamine induced dopaminergic neurotoxicity by flupirtine: microdialysis study on dopamine release and free radical generation.
2003 Feb
M channels containing KCNQ2 subunits modulate norepinephrine, aspartate, and GABA release from hippocampal nerve terminals.
2004 Jan 21
Efficacy of flupirtine on cognitive function in patients with CJD: A double-blind study.
2004 Mar 9
The potassium channel modulator flupirtine shifts the frequency-response function of hippocampal synapses to favour LTD in mice.
2004 Nov 11
Recent developments on KCNQ potassium channel openers.
2005
Retigabine and flupirtine exert neuroprotective actions in organotypic hippocampal cultures.
2006 Aug
[Many faces--one disease: fibromyalgia].
2007 Jul
Molecular expression and pharmacological identification of a role for K(v)7 channels in murine vascular reactivity.
2007 Jul
Flupirtine attenuates sodium nitroprusside-induced damage to retinal photoreceptors, in situ.
2007 Jul 12
[Analgesic and muscle tonus normalizing effect of flupirtine retard in chronic back pain].
2007 Oct 25
Systematic review of therapeutic interventions in human prion disease.
2008 Apr 8
K(+)-channel openers suppress epileptiform activities induced by 4-aminopyridine in cultured rat hippocampal neurons.
2008 Dec
Analgesic efficacy and tolerability of flupirtine vs. tramadol in patients with subacute low back pain: a double-blind multicentre trial*.
2008 Dec
Molecular pharmacology and therapeutic potential of neuronal Kv7-modulating drugs.
2008 Feb
Antihyperalgesic and analgesic properties of the N-methyl-D-aspartate (NMDA) receptor antagonist neramexane in a human surrogate model of neurogenic hyperalgesia.
2008 Jan
[Analgesic and muscle tonus normalizing effect of flupirtine retard in chronic back pain. Results of a standardized therapeutic evaluation applying objective methods for measuring pain pressure threshold, pain pressure tolerance and muscle tension].
2008 Jan 17
The efficacy of tetracyclines in peripheral and intracerebral prion infection.
2008 Mar 26
G-protein inwardly rectifying potassium channels are involved in the hypotensive effect of I1-imidazoline receptor selective ligands.
2008 May
Vascular KCNQ potassium channels as novel targets for the control of mesenteric artery constriction by vasopressin, based on studies in single cells, pressurized arteries, and in vivo measurements of mesenteric vascular resistance.
2008 May
Flupirtine as neuroprotective add-on therapy in autoimmune optic neuritis.
2008 Nov
Combination therapy with flupirtine and opioid: studies in rat pain models.
2008 Oct
Bimodal effects of the Kv7 channel activator retigabine on vascular K+ currents.
2008 Sep
Safety and efficacy of quinacrine in human prion disease (PRION-1 study): a patient-preference trial.
2009 Apr
Clinical trials for prion disease: difficult challenges, but hope for the future.
2009 Apr
KCNQ modulators reveal a key role for KCNQ potassium channels in regulating the tone of rat pulmonary artery smooth muscle.
2009 Apr
[Systematic review of the therapeutics for prion diseases].
2009 Aug
GDNF selectively induces microglial activation and neuronal survival in CA1/CA3 hippocampal regions exposed to NMDA insult through Ret/ERK signalling.
2009 Aug 3
Investigation of the in vitro metabolism of the analgesic flupirtine.
2009 Mar
Interference with bile salt export pump function is a susceptibility factor for human liver injury in drug development.
2010 Dec
Flupirtine may stop the progressive course of subacute sclerosing panencephalitis.
2010 Dec
Evidence of key tinnitus-related brain regions documented by a unique combination of manganese-enhanced MRI and acoustic startle reflex testing.
2010 Dec 15
Discrepancy between prevalence and perceived effectiveness of treatment methods in myofascial pain syndrome: results of a cross-sectional, nationwide survey.
2010 Feb 11
Green urine following exposure to flupirtine.
2010 Nov
M-type potassium channels modulate the intrinsic excitability of infralimbic neurons and regulate fear expression and extinction.
2010 Sep 15
Patents

Sample Use Guides

Flupirtine can be administered by oral and rectal routes. It is available as 50 and 100 mg for oral administration. Adult dose is 300–400 mg per day and can be increased to 600 mg per day. Dose in children is 150–200 mg per day in 3–4 divided doses. Rectal suppositories are administered in the dose range of 450–600 mg per day in adults and 150–250 mg per day in children.
Route of Administration: Other
Variations in the growth of U373 MG cells in 5 mM N-methyl-D-aspartate (NMDA), 1 mM flupirtine, and combined treatment indicated the antagonistic effects of NMDA and flupirtine on MG cell lines. The variation in the percentage of gated cell population in different cell cycle phases showed significant variations after 48 h of treatment.
Name Type Language
FLUPIRTINE
INN   MI   VANDF   WHO-DD  
INN  
Official Name English
ETHYL 2-AMINO-6-((P-FLUOROBENZYL)AMINO)-3-PYRIDINECARBAMATE
Common Name English
FLUPIRTINTE [VANDF]
Common Name English
flupirtine [INN]
Common Name English
FLUPIRTINE [MI]
Common Name English
FLUPIRTINE [VANDF]
Common Name English
Flupirtine [WHO-DD]
Common Name English
W-2964
Common Name English
CARBAMIC ACID, (2-AMINO-6-(((4-FLUOROPHENYL)METHYL)AMINO)-3-PYRIDINYL)-, ETHYL ESTER, (Z)-2-
Common Name English
Classification Tree Code System Code
WHO-ATC N02BG07
Created by admin on Wed Jul 05 23:37:50 UTC 2023 , Edited by admin on Wed Jul 05 23:37:50 UTC 2023
NCI_THESAURUS C241
Created by admin on Wed Jul 05 23:37:50 UTC 2023 , Edited by admin on Wed Jul 05 23:37:50 UTC 2023
WHO-VATC QN02BG07
Created by admin on Wed Jul 05 23:37:50 UTC 2023 , Edited by admin on Wed Jul 05 23:37:50 UTC 2023
Code System Code Type Description
CAS
56995-20-1
Created by admin on Wed Jul 05 23:37:50 UTC 2023 , Edited by admin on Wed Jul 05 23:37:50 UTC 2023
PRIMARY
FDA UNII
MOH3ET196H
Created by admin on Wed Jul 05 23:37:50 UTC 2023 , Edited by admin on Wed Jul 05 23:37:50 UTC 2023
PRIMARY
MERCK INDEX
M5491
Created by admin on Wed Jul 05 23:37:50 UTC 2023 , Edited by admin on Wed Jul 05 23:37:50 UTC 2023
PRIMARY Merck Index
RXCUI
25193
Created by admin on Wed Jul 05 23:37:50 UTC 2023 , Edited by admin on Wed Jul 05 23:37:50 UTC 2023
PRIMARY RxNorm
ECHA (EC/EINECS)
260-503-8
Created by admin on Wed Jul 05 23:37:50 UTC 2023 , Edited by admin on Wed Jul 05 23:37:50 UTC 2023
PRIMARY
MESH
C034161
Created by admin on Wed Jul 05 23:37:50 UTC 2023 , Edited by admin on Wed Jul 05 23:37:50 UTC 2023
PRIMARY
WIKIPEDIA
FLUPIRTINE
Created by admin on Wed Jul 05 23:37:50 UTC 2023 , Edited by admin on Wed Jul 05 23:37:50 UTC 2023
PRIMARY
DRUG CENTRAL
1215
Created by admin on Wed Jul 05 23:37:50 UTC 2023 , Edited by admin on Wed Jul 05 23:37:50 UTC 2023
PRIMARY
ChEMBL
CHEMBL255044
Created by admin on Wed Jul 05 23:37:50 UTC 2023 , Edited by admin on Wed Jul 05 23:37:50 UTC 2023
PRIMARY
PUBCHEM
53276
Created by admin on Wed Jul 05 23:37:50 UTC 2023 , Edited by admin on Wed Jul 05 23:37:50 UTC 2023
PRIMARY
EPA CompTox
DTXSID4048436
Created by admin on Wed Jul 05 23:37:50 UTC 2023 , Edited by admin on Wed Jul 05 23:37:50 UTC 2023
PRIMARY
EVMPD
SUB07732MIG
Created by admin on Wed Jul 05 23:37:50 UTC 2023 , Edited by admin on Wed Jul 05 23:37:50 UTC 2023
PRIMARY
INN
3976
Created by admin on Wed Jul 05 23:37:50 UTC 2023 , Edited by admin on Wed Jul 05 23:37:50 UTC 2023
PRIMARY
SMS_ID
100000080740
Created by admin on Wed Jul 05 23:37:50 UTC 2023 , Edited by admin on Wed Jul 05 23:37:50 UTC 2023
PRIMARY
DRUG BANK
DB06623
Created by admin on Wed Jul 05 23:37:50 UTC 2023 , Edited by admin on Wed Jul 05 23:37:50 UTC 2023
PRIMARY
NCI_THESAURUS
C72116
Created by admin on Wed Jul 05 23:37:50 UTC 2023 , Edited by admin on Wed Jul 05 23:37:50 UTC 2023
PRIMARY