FLUPIRTINE MALEATE

Possibly Marketed Outside US

Details

Stereochemistry	ACHIRAL
Molecular Formula	C15H17FN4O2.C4H4O4
Molecular Weight	420.3916
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	1
Charge	0

SHOW SMILES / InChI

Structure Search

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	No
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	No
Defined Stereocenters	0 / 0
E/Z Centers	1
Optical Activity	NONE

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/20839897 | https://www.ncbi.nlm.nih.gov/pubmed/22557738

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

Targets

Primary Target	Pharmacology	Condition	Potency
Glutamate [NMDA] receptor 125 Target ID: CHEMBL2094124 Sources: https://www.ncbi.nlm.nih.gov/pubmed/9510072 \| https://www.ncbi.nlm.nih.gov/pubmed/10599868	Antagonist 2849
KCNQ (Kv7) potassium channel 10 Target ID: CHEMBL2363063 Sources: https://www.ncbi.nlm.nih.gov/pubmed/20839897 \| https://www.ncbi.nlm.nih.gov/pubmed/9421279 \| https://www.ncbi.nlm.nih.gov/pubmed/23394517	Opener 34

Conditions

Condition	Modality	Targets	Highest Phase	Product
Acute (short-term) pain 4 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22557738 https://www.ncbi.nlm.nih.gov/pubmed/20839897	Primary		Approved 8583	Flupirtine Approved Use Treatment of acute pain in adults

C_max

Value	Dose	Analyte	Population
773 μg/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3200777/	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:	FLUPIRTINE serum	Homo sapiens population: HEALTHY age: ADULT sex: food status: UNKNOWN
722 μg/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3200777/	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:	FLUPIRTINE serum	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED
1116 μg/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3200777/	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:	FLUPIRTINE serum	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED
1977 μg/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3200777/	100 mg 3 times / day multiple, oral dose: 100 mg route of administration: Oral experiment type: MULTIPLE co-administered:	FLUPIRTINE serum	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED

AUC

Value	Dose	Analyte	Population
6070 μg × h/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3200777/	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:	FLUPIRTINE serum	Homo sapiens population: HEALTHY age: ADULT sex: food status: UNKNOWN
6656 μg × h/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3200777/	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:	FLUPIRTINE serum	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED
10346 μg × h/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3200777/	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:	FLUPIRTINE serum	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED
9991 μg × h/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3200777/	100 mg 3 times / day multiple, oral dose: 100 mg route of administration: Oral experiment type: MULTIPLE co-administered:	FLUPIRTINE serum	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED

T_1/2

Value	Dose	Analyte	Population
6.5 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3200777/	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:	FLUPIRTINE serum	Homo sapiens population: HEALTHY age: ADULT sex: food status: UNKNOWN
9.8 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3200777/	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:	FLUPIRTINE serum	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED
14 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3200777/	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:	FLUPIRTINE serum	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED
18.6 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3200777/	100 mg 3 times / day multiple, oral dose: 100 mg route of administration: Oral experiment type: MULTIPLE co-administered:	FLUPIRTINE serum	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED

Doses

Dose	Population	Adverse events
600 mg 1 times / day multiple, oral Higher than recommended Dose: 600 mg, 1 times / day Route: oral Route: multiple Dose: 600 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/22044433/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/22044433/	Disc. AE: Liver function test abnormal, ALT increased... AEs leading to discontinuation/dose reduction: Liver function test abnormal (6%) ALT increased (1.2%) ALT increased (1.2%) AST increased (1.2%) Rash (1.2%) Hypersensitivity (1.2%) Abdominal pain (1.2%) Vomiting (1.2%) Pyrexia (1.2%) Pruritus (1.2%) Sources: https://pubmed.ncbi.nlm.nih.gov/22044433/
400 mg 1 times / day multiple, oral Recommended Dose: 400 mg, 1 times / day Route: oral Route: multiple Dose: 400 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/22970658/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/22970658/	Disc. AE: Nausea, Dizziness... AEs leading to discontinuation/dose reduction: Nausea (0.8%) Dizziness (0.8%) Hyperhidrosis (0.8%) Urine color abnormal (0.8%) Sources: https://pubmed.ncbi.nlm.nih.gov/22970658/

AEs

AE	Significance	Dose	Population
ALT increased	1.2% Disc. AE	600 mg 1 times / day multiple, oral Higher than recommended Dose: 600 mg, 1 times / day Route: oral Route: multiple Dose: 600 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/22044433/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/22044433/
ALT increased	1.2% Disc. AE	600 mg 1 times / day multiple, oral Higher than recommended Dose: 600 mg, 1 times / day Route: oral Route: multiple Dose: 600 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/22044433/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/22044433/
AST increased	1.2% Disc. AE	600 mg 1 times / day multiple, oral Higher than recommended Dose: 600 mg, 1 times / day Route: oral Route: multiple Dose: 600 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/22044433/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/22044433/
Abdominal pain	1.2% Disc. AE	600 mg 1 times / day multiple, oral Higher than recommended Dose: 600 mg, 1 times / day Route: oral Route: multiple Dose: 600 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/22044433/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/22044433/
Hypersensitivity	1.2% Disc. AE	600 mg 1 times / day multiple, oral Higher than recommended Dose: 600 mg, 1 times / day Route: oral Route: multiple Dose: 600 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/22044433/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/22044433/
Pruritus	1.2% Disc. AE	600 mg 1 times / day multiple, oral Higher than recommended Dose: 600 mg, 1 times / day Route: oral Route: multiple Dose: 600 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/22044433/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/22044433/
Pyrexia	1.2% Disc. AE	600 mg 1 times / day multiple, oral Higher than recommended Dose: 600 mg, 1 times / day Route: oral Route: multiple Dose: 600 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/22044433/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/22044433/
Rash	1.2% Disc. AE	600 mg 1 times / day multiple, oral Higher than recommended Dose: 600 mg, 1 times / day Route: oral Route: multiple Dose: 600 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/22044433/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/22044433/
Vomiting	1.2% Disc. AE	600 mg 1 times / day multiple, oral Higher than recommended Dose: 600 mg, 1 times / day Route: oral Route: multiple Dose: 600 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/22044433/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/22044433/
Liver function test abnormal	6% Disc. AE	600 mg 1 times / day multiple, oral Higher than recommended Dose: 600 mg, 1 times / day Route: oral Route: multiple Dose: 600 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/22044433/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/22044433/
Dizziness	0.8% Disc. AE	400 mg 1 times / day multiple, oral Recommended Dose: 400 mg, 1 times / day Route: oral Route: multiple Dose: 400 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/22970658/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/22970658/
Hyperhidrosis	0.8% Disc. AE	400 mg 1 times / day multiple, oral Recommended Dose: 400 mg, 1 times / day Route: oral Route: multiple Dose: 400 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/22970658/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/22970658/
Nausea	0.8% Disc. AE	400 mg 1 times / day multiple, oral Recommended Dose: 400 mg, 1 times / day Route: oral Route: multiple Dose: 400 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/22970658/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/22970658/
Urine color abnormal	0.8% Disc. AE	400 mg 1 times / day multiple, oral Recommended Dose: 400 mg, 1 times / day Route: oral Route: multiple Dose: 400 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/22970658/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/22970658/

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1946 inhibitor 2252 activator 150	inhibitor 2438	inhibitor 2507	inhibitor 2217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP2C19 2057 CYP1A2 2153 MRP4 290 MRP3 246 BSEP 550 MRP2 499 UGT2B15 84 UGT2B7 197 UGT2B17 31	UGT1A1 479 P-gp 2052

Drug as perpetrator

Target	Modality	Activity
CYP2C19 2141	inhibitor 4027 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwzNjIyIiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDI1NTA0NCJ9fQ==	inconclusive [IC50 25.1189 uM]
CYP2C9 2497	inhibitor 4027 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwzMzk3IiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDI1NTA0NCJ9fQ==	inconclusive [IC50 25.1189 uM]
CYP1A2 2333	inhibitor 4027 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwzMzU2IiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDI1NTA0NCJ9fQ==	inconclusive [IC50 39.8107 uM]
MRP2 625	inhibitor 4027 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkw1NzQ4IiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDI1NTA0NCJ9fQ==	no [IC50 >133 uM]
MRP3 326	inhibitor 4027 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkw1OTE4IiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDI1NTA0NCJ9fQ==	no [IC50 >133 uM]
MRP4 345	inhibitor 4027 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwxNzQzMTI4IiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDI1NTA0NCJ9fQ==	no [IC50 >133 uM]
CYP3A4 2633	activator 342 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwzNDAiLCJ1c2VfY3VzdG9tX3F1ZXJ5Ijp0cnVlLCJzZWFyY2hfdGVybSI6IiIsInRleHRfZmlsdGVyIjoiQ0hFTUJMMjU1MDQ0In19	no
CYP2D6 2546	inhibitor 4027 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwyODkiLCJ1c2VfY3VzdG9tX3F1ZXJ5Ijp0cnVlLCJzZWFyY2hfdGVybSI6IiIsInRleHRfZmlsdGVyIjoiQ0hFTUJMMjU1MDQ0In19	yes [IC50 31.6228 uM]
BSEP 554	inhibitor 4027 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkw2MDIwIiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDI1NTA0NCJ9fQ==	yes [IC50 35.5 uM]
CYP3A4 2633	inhibitor 4027 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwzNDAiLCJ1c2VfY3VzdG9tX3F1ZXJ5Ijp0cnVlLCJzZWFyY2hfdGVybSI6IiIsInRleHRfZmlsdGVyIjoiQ0hFTUJMMjU1MDQ0In19	yes [IC50 7.9433 uM]
UGT2B15 84	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/25264565/	yes
UGT2B17 33	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/25264565/	yes
UGT2B7 210	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/25264565/	yes

Drug as victim

Target	Modality	Activity	Clinical evidence
P-gp 2052	substrate 4014 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/53276#section=BioAssay-Results Page: 82 \| 84	no
CYP3A4 1946	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/19074524/	weak
UGT1A1 479	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/25264565/	yes	yes (pharmacogenomic study) Comment: The 7/7 promoter polymorphism of UGT1A1 did not influence metabolic disposition of flupirtine. Sources: https://pubmed.ncbi.nlm.nih.gov/25264565/

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 2263	inhibitor 2237 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwyNDAiLCJ1c2VfY3VzdG9tX3F1ZXJ5Ijp0cnVlLCJzZWFyY2hfdGVybSI6IiIsInRleHRfZmlsdGVyIjoiQ0hFTUJMMTI1Njc1MiJ9fQ==

PubMed

Title	Date	PubMed
[2010 German Pain Congress. Backache - new data, specific muscle etiology and targeted therapy].	2010-12-16	21294372
Evidence of key tinnitus-related brain regions documented by a unique combination of manganese-enhanced MRI and acoustic startle reflex testing.	2010-12-15	21179508
[Musculoskeletal pain. Pain relief with muscle relaxant].	2010-12-02	21222334
Interference with bile salt export pump function is a susceptibility factor for human liver injury in drug development.	2010-12	20829430
Flupirtine may stop the progressive course of subacute sclerosing panencephalitis.	2010-12	20702046
Enhancement of axonal potassium conductance reduces nerve hyperexcitability in an in vitro model of oxaliplatin-induced acute neuropathy.	2010-12	20670646
Green urine following exposure to flupirtine.	2010-11	20970027
Flupirtine in pain management: pharmacological properties and clinical use.	2010-10	20839897
M-type potassium channels modulate the intrinsic excitability of infralimbic neurons and regulate fear expression and extinction.	2010-09-15	20844133
Positive reinforcing effects of flupirtine--two case reports.	2010-08-16	20362025
[IGOST guideline for pharmacotherapy of low back pain].	2010-08-12	20828068
The Kv7 potassium channel activator flupirtine affects clinical excitability parameters of myelinated axons in isolated rat sural nerve.	2010-03	20433607
Discrepancy between prevalence and perceived effectiveness of treatment methods in myofascial pain syndrome: results of a cross-sectional, nationwide survey.	2010-02-11	20149248
CNSB004 (Leconotide) causes antihyperalgesia without side effects when given intravenously: a comparison with ziconotide in a rat model of diabetic neuropathic pain.	2010-02	20002322
Neuronal potassium channel openers in the management of epilepsy: role and potential of retigabine.	2010	22291509
[New approaches to the treatment of chronic daily headache].	2010	21183903
The M-channel blocker linopirdine is an agonist of the capsaicin receptor TRPV1.	2010	21099148
[Efficient treatment of chronic backache].	2009-12-10	20088326
Efficacy and safety of bilateral continuous theta burst stimulation (cTBS) for the treatment of chronic tinnitus: design of a three-armed randomized controlled trial.	2009-08-21	19698089
GDNF selectively induces microglial activation and neuronal survival in CA1/CA3 hippocampal regions exposed to NMDA insult through Ret/ERK signalling.	2009-08-03	19649251
[Systematic review of the therapeutics for prion diseases].	2009-08	19697882
Treatment with the Kv7 potassium channel activator flupirtine is beneficial in two independent mouse models of pulmonary hypertension.	2009-08	19508393
KCNQ currents and their contribution to resting membrane potential and the excitability of interstitial cells of Cajal from the guinea pig bladder.	2009-07	19450820
A girl with headache, confusion and green urine.	2009-07	19252777
Flupirtine: pharmacology and clinical applications of a nonopioid analgesic and potentially neuroprotective compound.	2009-06	19505216
An in vitro screening cascade to identify neuroprotective antioxidants in ALS.	2009-04-15	19439221
Neural KCNQ (Kv7) channels.	2009-04	19298256
Safety and efficacy of quinacrine in human prion disease (PRION-1 study): a patient-preference trial.	2009-04	19278902
Clinical trials for prion disease: difficult challenges, but hope for the future.	2009-04	19278901
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.	2009-04	19187447
KCNQ modulators reveal a key role for KCNQ potassium channels in regulating the tone of rat pulmonary artery smooth muscle.	2009-04	19151245
A KCNQ channel opener for experimental neonatal seizures and status epilepticus.	2009-03	19334075
Investigation of the in vitro metabolism of the analgesic flupirtine.	2009-03	19074524
Therapeutic trials in human transmissible spongiform encephalo-pathies: recent advances and problems to address.	2009-02	19200019
Enhancing m currents: a way out for neuropathic pain?	2009	19680469
K(+)-channel openers suppress epileptiform activities induced by 4-aminopyridine in cultured rat hippocampal neurons.	2008-12	19075508
Analgesic efficacy and tolerability of flupirtine vs. tramadol in patients with subacute low back pain: a double-blind multicentre trial*.	2008-12	19032134
Flupirtine as neuroprotective add-on therapy in autoimmune optic neuritis.	2008-11	18832577
Combination therapy with flupirtine and opioid: open-label case series in the treatment of neuropathic pain associated with cancer.	2008-10	18950447
Combination therapy with flupirtine and opioid: studies in rat pain models.	2008-10	18950446
Bimodal effects of the Kv7 channel activator retigabine on vascular K+ currents.	2008-09	18536747
G-protein inwardly rectifying potassium channels are involved in the hypotensive effect of I1-imidazoline receptor selective ligands.	2008-05	18398346
[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].	2008-01-17	18402240
[Efficacy of katadolon and cranial-spine electromagnetic neuromodulation in patients with discogenic radiculopathy].	2008	19097315
Melatonin counteracts ischemia-induced apoptosis in human retinal pigment epithelial cells.	1998-11	9804146
Antiparkinsonian and other motor effects of flupirtine alone and in combination with dopaminergic drugs.	1997-05-26	9185829
Pharmacological mechanisms of action of flupirtine: a novel, centrally acting, nonopioid analgesic evaluated by its discriminative effects in the rat.	1988-09	2901483
Pharmacokinetics of flupirtine in elderly volunteers and in patients with moderate renal impairment.	1988-05	3200777
[General pharmacologic studies on the analgesic flupirtine].	1985	4039152
Quantitation of flupirtine and its active acetylated metabolite by reversed-phase high-performance liquid chromatography using fluorometric detection.	1984-01-13	6707137

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: Other

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 `Mon Mar 31 18:25:48 GMT 2025` Edited by `admin` on `Mon Mar 31 18:25:48 GMT 2025`
Record UNII	0VCI53PK4A
Record Status	`Validated (UNII)`
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Name

Type

Language

D-9998

Preferred Name

English

FLUPIRTINE MALEATE

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

FLUPIRTINTE MALEATE [VANDF]

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 [WHO-DD]

Common 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