Flupirtine

OBJECTIVE: To investigate clinical characteristics and risk factors of patients with Flupirtine-induced liver cirrhosis complicated with upper gastrointestinal bleeding. METHODS: A total of 116 patients with liver cirrhosis admitted to our hospital from July 2018 to July 2019 were selected and divided into bleeding group (liver cirrhosis complicated with upper gastrointestinal bleeding, n = 71) and non-bleeding group (liver cirrhosis, n = 45). The clinical data of patients in the two groups were collected, including general data, liver function, urinalysis, coagulation function and imaging data...

Recent studies in our lab have shown that the KV 7 channel activator, flupirtine, inhibits colonic epithelial Cl- secretion through effects on submucosal neurons of the enteric nervous system (ENS). We hypothesized that flupirtine would also stimulate Na+ absorption as a result of reduced secretory ENS input to the epithelium. To test this hypothesis, unidirectional 22 Na+ fluxes were measured under voltage-clamped conditions. Pharmacological approaches using an Ussing-style recording chamber, combined immunofluorescence microscopy techniques were used to determine the effect of flupirtine on active Na+ transport in the rat colon...

The rising interest in Kv7 modulators originates from their ability to evoke fundamental electrophysiological perturbations in a tissue-specific manner. A large number of therapeutic applications are, in part, based on the clinical experience with two broad-spectrum Kv7 agonists, flupirtine and retigabine . Since precise molecular structures of human Kv7 channel subtypes in closed and open states have only very recently started to emerge, computational studies have traditionally been used to analyze binding modes and direct the development of more potent and selective Kv7 modulators with improved safety profiles...

KV 7 (KCNQ) K+ channels are expressed in many neuronal populations, and play an important role in regulating membrane potential by generating a hyper-polarizing K+ current and decreasing cell excitability. However, the role of KV 7 channels in the neural regulation of intestinal epithelial Cl- secretion is not known. Cl- secretion in mouse distal colon was measured as a function of short circuit current (ISC ), while pharmacological approaches were used to test the hypothesis that activation of KV 7 channels in enteric neurons would inhibit epithelial Cl- secretion...

Native M-current is a low-threshold, slowly activating potassium current that exerts an inhibitory control over neuronal excitability. The M-channel is primarily co-assembled by heterotetrameric Kv7.2/KCNQ2 and Kv7.3/KCNQ3 subunits that are specifically expressed in the brain and peripheral nociceptive and visceral sensory neurons in the spinal cord. Reduction of M-channel function leads to neuronal hyperexcitability that defines the fundamental mechanism of neurological disorders such as epilepsy and pain, indicating that pharmacological activation of Kv7/KCNQ/M-channels may serve the basis for the therapy...

Transmembrane serine protease (TMPRSS2) plays an oncogenic role in prostate cancer as the fusion gene with ERG, and has also been demonstrated to be essential for the cellular entry of severe acute respiratory syndrome coronaviruses (SARS-CoV). Thus, targeting TMPRSS2 is a promising strategy for therapies against both prostate cancer and coronavirus infection. Although Nafamostat and Camostat have been identified as TMPRSS2 inhibitors, severe side effects such as cerebral hemorrhage, anaphylactoid reaction, and cardiac arrest shock greatly hamper their clinical use...

Since 1955, several alkyl-carbamates have been developed for the treatment of anxiety and epilepsy, including meprobamate, flupirtine, felbamate, retigabine, carisbamate, and cenobamate. They have each enjoyed varying levels of success as antiseizure drugs; however, they have all been plagued by the emergence of serious and sometimes life-threatening adverse events. In this review, we compare and contrast their predominant molecular mechanisms of action, their antiseizure profile, and where possible, their clinical efficacy...

Acute intoxications are common causes of admission to the Emergency Department (ED). Flupirtine is a non-opioid analgesic, originally used for acute and chronic pain. Because of several reports of severe liver toxicity, its use was limited to acute pain in 2013 by the European Medicines Agency. Although withdrawn from the European market in March 2018, there are still flupirtine tablets in many households, and most people are unaware of the hazards they might be facing. A 58-year-old man was admitted to the ED after a suicide attempt with 1 g of flupirtine...

INTRODUCTION: Treating chronic low back pain (LBP) can be challenging, and the most effective pharmacological therapy is controversial. The present systematic review investigated the efficacy of various pharmacological compounds to achieve pain relief and improve disability in chronic LBP patients. The present study focused on acetaminophen, amoxicillin, flupirtine, baclofen, tryciclic antidepressants (TCAs), duloxetine, topiramate, gabapentinoids, non-steroid anti-inflammatory drugs (NSAIDs) and opioids...

Flupirtine is a non-opioid centrally acting analgesic that has been in clinical use, and is reported to act on neuronal ion channels and neurotransmitter receptors. However, its action on emotional aspects of pain is still unknown. In this study, we examined whether flupirtine has anxiolytic action and assayed its direct actions on the anterior cingulate cortex (ACC) at the single neuronal and synaptic levels. Anti-nociceptive and anxiolytic effects of flupirtine were evaluated by von Frey test and elevated plus-maze (EPM) in adult rats...

CLN3 disease is a fatal neurodegenerative disorder affecting children. Hallmarks include brain atrophy, accelerated neuronal apoptosis, and ceramide elevation. Treatment regimens are supportive, highlighting the importance of novel, disease-modifying drugs. Flupirtine and its new allyl carbamate derivative (compound 6) confer neuroprotective effects in CLN3-deficient cells. This study lays the groundwork for investigating beneficial effects in Cln3Δex7/8 mice. WT/ Cln3Δex7/8 mice received flupirtine/compound 6/vehicle for 14 weeks...

BACKGROUND: The prevalence of chronic pelvic pain of 11.8% in the general population underlines the importance of this disease. However, the specific diagnostics and therapy of the muscles of this region are not yet part of the standard examination. The following study examines the effects of specific diagnostics and therapy on myofascial chronic pelvic pain. OBJECTIVES: The effectiveness of targeted diagnostics and multimodal therapy in the context of chronic pelvic pain and the need for a complementary drug adjustment...

OBJECTIVES: Acute drug-induced liver failure is a rare indication for liver transplant. There is only one case of flupirtine-induced liver failure requiring transplant in the literature. In February 2018, the European Medicines Agency issued a withdrawal of approval for flupirtine medication in European countries as a result of the risk of acute liver failure. MATERIALS AND METHODS: The aim of this study was a German-wide collection of data regarding patients with liver transplant as a result of flupirtine-associated liver failure...

Introduction : Important drug safety issues are evaluated through a referral procedure in the EU by the Pharmacovigilance Risk Assessment Committee (PRAC) within the European Medicines Agency. We aim to describe all safety-related referrals assessed by the PRAC by June 2019. Methods : Publicly available data on safety issues assessed through referral procedures that reached a final decision during July 2012-June 2019 were identified, analyzed and classified according to predefined criteria. Results : Fifty-one safety issues were assessed by PRAC for 45 medicines/combinations/therapeutic classes during this timeframe...

INTRODUCTION: Gout arthritis is an inflammatory disease characterized by severe acute pain. The goal of pharmacological gout arthritis treatments is to reduce pain, and thereby increase the patient's quality of life. The Kv7/M channel activators retigabine and flupirtine show analgesic efficacy in animal models of osteoarthritic pain. We hypothesized that these drugs may also alleviate gout arthritis pain. OBJECTIVE: To determine the effects of retigabine and flupirtine on pain behavior associated with monosodium urate (MSU)-induced gout arthritis...

BACKGROUND: Hypoxia-ischemia (HI) is the most common cause of brain injury in newborns and the survivors often develop cognitive and sensorimotor disabilities that undermine the quality of life. In the current study, we examined the effectiveness of flupirtine, a potassium channel opener, shown previously in an animal model to have strong anti-neonatal-seizure efficacy, to provide neuroprotection and alleviate later-life disabilities caused by neonatal hypoxic-ischemic injury. METHODS: The rats were treated with a single dose of flupirtine for 4 days following HI induction in 7-day-old rats...

Perampanel (PER) is a selective blocker of AMPA receptors showing efficacy in treating various epileptic disorders including brain tumor-related epilepsy and also potential in treating motor neuron disease. However, besides its inhibition of AMPA-induced currents, whether PER has any other direct ionic effects in different types of neurons remains largely unknown. We investigated the effects of PER and related compounds on ionic currents in different types of cells, including hippocampal mHippoE-14 neurons, motor neuron-like NSC-34 cells and U87 glioma cells...

This review summarizes the efforts of our laboratories to develop a mechanism-based therapy for the treatment of organophosphate (OP) nerve agent-induced seizures. Organophosphate poisoning can occur during warfare and terrorist attacks and in the civilian sphere because of intentional or unintentional poisoning. Persons exposed to OPs experience seizures. We developed animal models of OP poisoning and then evaluated the effects of OP on excitatory α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor-mediated glutamatergic neurotransmission in the hippocampus using patch-clamp electrophysiology...

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Supercritical fluid chromatography (SFC) holds the potential to become an orthogonal method to HPLC/UHPLC in xenobiotic metabolism studies, due to its outstanding capacity to simultaneously separate highly similar (as HPLC) and physicochemically different analytes (problematic using HPLC). Paucity of guideline-conform validation, however, has been a major obstacle to clinical application of SFC, even in cases where biotransformation yields chemically dissimilar metabolites that require more than one HPLC method for comprehensive analysis...