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

Details

Stereochemistry ACHIRAL
Molecular Formula C15H17FN4O2.C4H4O4
Molecular Weight 420.3916
Optical Activity UNSPECIFIED
Defined Stereocenters 0 / 0
E/Z Centers 1
Charge 0

SHOW SMILES / InChI
Structure of FLUPIRTINE MALEATE

SMILES

OC(=O)\C=C/C(O)=O.CCOC(=O)NC1=C(N)N=C(NCC2=CC=C(F)C=C2)C=C1

InChI

InChIKey=DPYIXBFZUMCMJM-BTJKTKAUSA-N
InChI=1S/C15H17FN4O2.C4H4O4/c1-2-22-15(21)19-12-7-8-13(20-14(12)17)18-9-10-3-5-11(16)6-4-10;5-3(6)1-2-4(7)8/h3-8H,2,9H2,1H3,(H,19,21)(H3,17,18,20);1-2H,(H,5,6)(H,7,8)/b;2-1-

HIDE SMILES / InChI

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

Molecular Formula C4H4O4
Molecular Weight 116.0722
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry
Defined Stereocenters 0 / 0
E/Z Centers 1
Optical Activity NONE

Description

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.

CNS Activity

Originator

Approval Year

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Flupirtine
PubMed

PubMed

TitleDatePubMed
Quantitation of flupirtine and its active acetylated metabolite by reversed-phase high-performance liquid chromatography using fluorometric detection.
1984 Jan 13
[General pharmacologic studies on the analgesic flupirtine].
1985
Pharmacokinetics of flupirtine in elderly volunteers and in patients with moderate renal impairment.
1988 May
Pharmacological mechanisms of action of flupirtine: a novel, centrally acting, nonopioid analgesic evaluated by its discriminative effects in the rat.
1988 Sep
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
Flupirtine blocks apoptosis in batten patient lymphoblasts and in human postmitotic CLN3- and CLN2-deficient neurons.
2002 Apr
Treatment of spasticity.
2002 Jun
The potassium channel modulator flupirtine shifts the frequency-response function of hippocampal synapses to favour LTD in mice.
2004 Nov 11
Tumor-necrosis-factor-related apoptosis-inducing-ligand (TRAIL)-mediated death of neurons in living human brain tissue is inhibited by flupirtine-maleate.
2005 Oct
[The use of katadolon in patients with spondylogenic dorsalgia].
2006
[Use of katadolon in the treatment of abuse headache].
2006
HIV neurotoxicity: potential therapeutic interventions.
2006
[The use of katadolon (flupirtine) in the treatment of lower back pain].
2006
KCNQ/M-currents contribute to the resting membrane potential in rat visceral sensory neurons.
2006 Aug 15
The use of flupirtine in treatment of tinnitus.
2006 Dec
[Backache is often caused by strained muscles].
2006 May 25
Antidystonic effects of Kv7 (KCNQ) channel openers in the dt sz mutant, an animal model of primary paroxysmal dystonia.
2006 Nov
[Many faces--one disease: fibromyalgia].
2007 Jul
Flupirtine attenuates sodium nitroprusside-induced damage to retinal photoreceptors, in situ.
2007 Jul 12
Vasopressin stimulates action potential firing by protein kinase C-dependent inhibition of KCNQ5 in A7r5 rat aortic smooth muscle cells.
2007 Mar
[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
Analgesic efficacy and tolerability of flupirtine vs. tramadol in patients with subacute low back pain: a double-blind multicentre trial*.
2008 Dec
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
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
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
Activation of pre-synaptic M-type K+ channels inhibits [3H]D-aspartate release by reducing Ca2+ entry through P/Q-type voltage-gated Ca2+ channels.
2009 Apr
An in vitro screening cascade to identify neuroprotective antioxidants in ALS.
2009 Apr 15
Treatment with the Kv7 potassium channel activator flupirtine is beneficial in two independent mouse models of pulmonary hypertension.
2009 Aug
Therapeutic trials in human transmissible spongiform encephalo-pathies: recent advances and problems to address.
2009 Feb
KCNQ currents and their contribution to resting membrane potential and the excitability of interstitial cells of Cajal from the guinea pig bladder.
2009 Jul
A girl with headache, confusion and green urine.
2009 Jul
A KCNQ channel opener for experimental neonatal seizures and status epilepticus.
2009 Mar
Neuronal potassium channel openers in the management of epilepsy: role and potential of retigabine.
2010
[New approaches to the treatment of chronic daily headache].
2010
The M-channel blocker linopirdine is an agonist of the capsaicin receptor TRPV1.
2010
[IGOST guideline for pharmacotherapy of low back pain].
2010 Aug 12
Interference with bile salt export pump function is a susceptibility factor for human liver injury in drug development.
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
[2010 German Pain Congress. Backache - new data, specific muscle etiology and targeted therapy].
2010 Dec 16
[Musculoskeletal pain. Pain relief with muscle relaxant].
2010 Dec 2
The Kv7 potassium channel activator flupirtine affects clinical excitability parameters of myelinated axons in isolated rat sural nerve.
2010 Mar
Green urine following exposure to flupirtine.
2010 Nov
Flupirtine in pain management: pharmacological properties and clinical use.
2010 Oct
M-type potassium channels modulate the intrinsic excitability of infralimbic neurons and regulate fear expression and extinction.
2010 Sep 15
Patents

Sample Use Guides

In Vivo Use Guide
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: oral, rectal
In Vitro Use Guide
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.
Substance Class Chemical
Created
by admin
on Tue Oct 22 00:19:50 UTC 2019
Edited
by admin
on Tue Oct 22 00:19:50 UTC 2019
Record UNII
0VCI53PK4A
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
FLUPIRTINE MALEATE
MART.   MI   USAN   VANDF   WHO-DD  
USAN  
Official Name English
FLUPIRTINE MALEATE [USAN]
Common Name English
CARBAMIC ACID, (2-AMINO-6-(((4-FLUOROPHENYL)METHYL)AMINO)-3-PYRIDINYL)-, ETHYL ESTER, (Z)-2-BUTENEDIOATE (1:1)
Systematic Name English
D-9998
Code English
FLUPIRTINTE MALEATE [VANDF]
Common Name English
FLUPIRTINE MALEATE [WHO-DD]
Common Name English
FLUPIRTINE MALEATE [MART.]
Common Name English
ETHYL 2-AMINO-6-((P-FLUOROBENZYL)AMINO)-3-PYRIDINECARBAMATE MALEATE (1:1)
Systematic Name English
FLUPIRTINE MALEATE [VANDF]
Common Name English
FLUPIRTINE MALEATE [MI]
Common Name English
W-2964M
Code English
Classification Tree Code System Code
NCI_THESAURUS C241
Created by admin on Tue Oct 22 00:19:50 UTC 2019 , Edited by admin on Tue Oct 22 00:19:50 UTC 2019
Code System Code Type Description
MERCK INDEX
M5491
Created by admin on Tue Oct 22 00:19:50 UTC 2019 , Edited by admin on Tue Oct 22 00:19:50 UTC 2019
PRIMARY Merck Index
NCI_THESAURUS
C72785
Created by admin on Tue Oct 22 00:19:50 UTC 2019 , Edited by admin on Tue Oct 22 00:19:50 UTC 2019
PRIMARY
ECHA (EC/EINECS)
278-225-0
Created by admin on Tue Oct 22 00:19:50 UTC 2019 , Edited by admin on Tue Oct 22 00:19:50 UTC 2019
PRIMARY
CAS
75507-68-5
Created by admin on Tue Oct 22 00:19:50 UTC 2019 , Edited by admin on Tue Oct 22 00:19:50 UTC 2019
PRIMARY
RXCUI
236774
Created by admin on Tue Oct 22 00:19:50 UTC 2019 , Edited by admin on Tue Oct 22 00:19:50 UTC 2019
PRIMARY RxNorm
EPA CompTox
75507-68-5
Created by admin on Tue Oct 22 00:19:50 UTC 2019 , Edited by admin on Tue Oct 22 00:19:50 UTC 2019
PRIMARY
PUBCHEM
6435335
Created by admin on Tue Oct 22 00:19:50 UTC 2019 , Edited by admin on Tue Oct 22 00:19:50 UTC 2019
PRIMARY
ChEMBL
CHEMBL255044
Created by admin on Tue Oct 22 00:19:50 UTC 2019 , Edited by admin on Tue Oct 22 00:19:50 UTC 2019
PRIMARY
EVMPD
SUB02234MIG
Created by admin on Tue Oct 22 00:19:50 UTC 2019 , Edited by admin on Tue Oct 22 00:19:50 UTC 2019
PRIMARY
Related Record Type Details
PARENT -> SALT/SOLVATE
PARENT -> SALT/SOLVATE
Related Record Type Details
ACTIVE MOIETY