CAS 75507-68-5|Flupirtine maleate

Introduction：Basic information about CAS 75507-68-5|Flupirtine maleate, including its chemical name, molecular formula, synonyms, physicochemical properties, and safety information, etc.

Table of Contents

1. Names
2. Flupirtine maleate BiologicalActivity
3. Chemical & Physical Properties
4. Safety Information
5. Customs
6. Articles27
7. Synonyms

Common Name	Flupirtine maleate
CAS Number	75507-68-5	Molecular Weight	420.392
Density	1.35 g/cm3	Boiling Point	434.9ºC at 760 mmHg
Molecular Formula	C₁₉H₂₁FN₄O₆	Melting Point	186-188ºC
MSDS	ChineseUSA	Flash Point	216.8ºC

Names

Name	Flupirtine Maleate Salt
Synonym	More Synonyms

Flupirtine maleate BiologicalActivity

Description	Flupirtine Maleate(D 9998) is a selective neuronal potassium channel opener that also has NMDA receptor antagonist properties.IC50 Value: Target: Potassium channel; NMDA receptorin vitro: High concentrations of flupirtine antagonized inward currents to NMDA(200 microM) at -70 mV with an lC50 against steady-state responses of 182.1+/-12.1 microM. The effects of flupirtine were voltage-independent and not associated with receptor desensitization making actions within the NMDA receptor channel or at the glycine modulatory site unlikely. NMDA receptor antagonism probably has little relevance for the clinical efficacy of flupirtine as the concentrations needed were far higher than those achieved in clinical practice. However, the activation of a G-protein-regulated inwardly rectifying K+ channel was identified as an interesting molecular target site of flupirtine. In the next stage, the central nervous spectrum of action of experimental K+ channel openers (PCO) was considered. As far as they have been studied, experimental K+ channel openers display a spectrum of action comparable to that of flupirtine [1]. Therapeutic flupirtine concentrations (≤10 μM) did not affect voltage-gated Na(+) or Ca(2+) channels, inward rectifier K(+) channels, nicotinic acetylcholine receptors, glycine or ionotropic glutamate receptors. Flupirtine shifted the gating of K(V)7 K(+) channels to more negative potentials and the gating of GABA(A) receptors to lower GABA concentrations [2]. Cell exposure to flupirtine decreased the amplitude of delayed rectifier K(+) current (I(K(DR))) with a concomitant raise in current inactivation in NSC-34 neuronal cells [4].in vivo: Rats were trained to discriminate the novel analgesic flupirtine (10.0 mg/kg i.p., 10 min) from no drug under a two-choice fixed-ratio 5 shock-termination schedule. Flupirtine yielded a dose-response curve with an ED50 of 3.87 mg/kg. The opioid analgesics pentazocine, codeine and tramadol failed to produce flupirtine appropriate responding. The opioid antagonist naltrexone did not antagonize the discriminative effects of flupirtine [3]. Both morphine (ED50=0.74 mg/kg) and flupirtine (ED50=3.32 mg/kg) caused dose-related anti-hyperalgesia at doses that did not cause sedation [5]. Toxicity: Based on study-end data, hepatotoxicity was detected in 31% of patients receiving flupirtine for ≥ 6 weeks [6].
Related Catalog	Signaling Pathways >>Membrane Transporter/Ion Channel >>iGluRSignaling Pathways >>Neuronal Signaling >>iGluRSignaling Pathways >>Membrane Transporter/Ion Channel >>Potassium ChannelResearch Areas >>Neurological Disease
References	[1]. Yeung et al (2007) Molecular expression and pharmacological identification of a role for Kv7 channels in murine vascular reactivity. Br.J.Pharmacol. 151 758. [2]. Gordon R, Sofia RD, Diamantis W.Effect of flupirtine maleate on the nociceptive pathway, EEG, evoked potentials and polysynaptic reflexes in laboratory animals.Postgrad Med J. 1987;63 Suppl 3:49-55. [3]. Hedges A, Warrington SJ, Turner P, Niebch G.Flupirtine maleate and antipyrine half-life.Eur J Clin Pharmacol. 1987;33(4):437. [4]. Powell-Jackson P, Williams R.Use of flupirtine maleate as an analgesic in patients with liver disease.Br J Clin Pract. 1985 Feb;39(2):63-6. [5]. Diamantis W, Gordon R, Sofia RD.Analgesic activity following combined oral administration of flupirtine maleate and peripherally acting analgesics in mice and rats.Postgrad Med J. 1987;63 Suppl 3:29-34.

Description

Flupirtine Maleate(D 9998) is a selective neuronal potassium channel opener that also has NMDA receptor antagonist properties.IC50 Value: Target: Potassium channel; NMDA receptorin vitro: High concentrations of flupirtine antagonized inward currents to NMDA(200 microM) at -70 mV with an lC50 against steady-state responses of 182.1+/-12.1 microM. The effects of flupirtine were voltage-independent and not associated with receptor desensitization making actions within the NMDA receptor channel or at the glycine modulatory site unlikely. NMDA receptor antagonism probably has little relevance for the clinical efficacy of flupirtine as the concentrations needed were far higher than those achieved in clinical practice. However, the activation of a G-protein-regulated inwardly rectifying K+ channel was identified as an interesting molecular target site of flupirtine. In the next stage, the central nervous spectrum of action of experimental K+ channel openers (PCO) was considered. As far as they have been studied, experimental K+ channel openers display a spectrum of action comparable to that of flupirtine [1]. Therapeutic flupirtine concentrations (≤10 μM) did not affect voltage-gated Na(+) or Ca(2+) channels, inward rectifier K(+) channels, nicotinic acetylcholine receptors, glycine or ionotropic glutamate receptors. Flupirtine shifted the gating of K(V)7 K(+) channels to more negative potentials and the gating of GABA(A) receptors to lower GABA concentrations [2]. Cell exposure to flupirtine decreased the amplitude of delayed rectifier K(+) current (I(K(DR))) with a concomitant raise in current inactivation in NSC-34 neuronal cells [4].in vivo: Rats were trained to discriminate the novel analgesic flupirtine (10.0 mg/kg i.p., 10 min) from no drug under a two-choice fixed-ratio 5 shock-termination schedule. Flupirtine yielded a dose-response curve with an ED50 of 3.87 mg/kg. The opioid analgesics pentazocine, codeine and tramadol failed to produce flupirtine appropriate responding. The opioid antagonist naltrexone did not antagonize the discriminative effects of flupirtine [3]. Both morphine (ED50=0.74 mg/kg) and flupirtine (ED50=3.32 mg/kg) caused dose-related anti-hyperalgesia at doses that did not cause sedation [5]. Toxicity: Based on study-end data, hepatotoxicity was detected in 31% of patients receiving flupirtine for ≥ 6 weeks [6].

Related Catalog

Signaling Pathways >>Membrane Transporter/Ion Channel >>iGluRSignaling Pathways >>Neuronal Signaling >>iGluRSignaling Pathways >>Membrane Transporter/Ion Channel >>Potassium ChannelResearch Areas >>Neurological Disease

References

[1]. Yeung et al (2007) Molecular expression and pharmacological identification of a role for Kv7 channels in murine vascular reactivity. Br.J.Pharmacol. 151 758.

[2]. Gordon R, Sofia RD, Diamantis W.Effect of flupirtine maleate on the nociceptive pathway, EEG, evoked potentials and polysynaptic reflexes in laboratory animals.Postgrad Med J. 1987;63 Suppl 3:49-55.

[3]. Hedges A, Warrington SJ, Turner P, Niebch G.Flupirtine maleate and antipyrine half-life.Eur J Clin Pharmacol. 1987;33(4):437.

[4]. Powell-Jackson P, Williams R.Use of flupirtine maleate as an analgesic in patients with liver disease.Br J Clin Pract. 1985 Feb;39(2):63-6.

[5]. Diamantis W, Gordon R, Sofia RD.Analgesic activity following combined oral administration of flupirtine maleate and peripherally acting analgesics in mice and rats.Postgrad Med J. 1987;63 Suppl 3:29-34.

Chemical & Physical Properties

Density	1.35 g/cm3
Boiling Point	434.9ºC at 760 mmHg
Melting Point	186-188ºC
Molecular Formula	C₁₉H₂₁FN₄O₆
Molecular Weight	420.392
Flash Point	216.8ºC
Exact Mass	420.144501
PSA	170.59000
LogP	2.71190
InChIKey	DPYIXBFZUMCMJM-BTJKTKAUSA-N
SMILES	CCOC(=O)Nc1ccc(NCc2ccc(F)cc2)nc1N.O=C(O)C=CC(=O)O
Storage condition	2-8°C
Water Solubility	DMSO: soluble >20mg/mL

Safety Information

Personal Protective Equipment	Eyeshields;Gloves;type N95 (US);type P1 (EN143) respirator filter
Hazard Codes	Xn
Safety Phrases	22-24/25
RIDADR	NONH for all modes of transport
RTECS	EY8555800
HS Code	2942000000

Customs

HS Code	2942000000

Articles27

Role of Kv7 channels in responses of the pulmonary circulation to hypoxia.

Am. J. Physiol. Lung Cell. Mol. Physiol. 308(1) , L48-57, (2015)

Hypoxic pulmonary vasoconstriction (HPV) is a beneficial mechanism that diverts blood from hypoxic alveoli to better ventilated areas of the lung, but breathing hypoxic air causes the pulmonary circul...

M channel enhancers and physiological M channel block.

J. Physiol. 590(Pt 4) , 793-807, (2012)

M-type (Kv7, KCNQ) K(+) channels control the resting membrane potential of many neurons, including peripheral nociceptive sensory neurons. Several M channel enhancers were suggested as prospective ana...

M-type potassium channels modulate Schaffer collateral-CA1 glutamatergic synaptic transmission.

J. Physiol. 590(Pt 16) , 3953-64, (2012)

Previous studies have suggested that muscarinic receptor activation modulates glutamatergic transmission. M-type potassium channels mediate the effects of muscarinic activation in the hippocampus, and...

Synonyms

Katadolon

Ethyl {2-amino-6-[(4-fluorobenzyl)amino]pyridin-3-yl}carbamate (2Z)-but-2-enedioate (1:1)

2-Amino-6-[[(4-fluorophenyl)methyl]amino]-3-pyridinyl]-carbamic acid ethyl ester maleate

(Z)-but-2-enedioic acid,ethyl N-[2-amino-6-[(4-fluorophenyl)methylamino]pyridin-3-yl]carbamate

Ethyl {2-amino-6-[(4-fluorobenzyl)amino]-3-pyridinyl}carbamate (2Z)-2-butenedioate (1:1)

Carbamic acid, N-[2-amino-6-[[(4-fluorophenyl)methyl]amino]-3-pyridinyl]-, ethyl ester, (2Z)-2-butenedioate (1:1)

Flupirtine maleate

Flupirtine (Maleate)

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