Search results for "Flupirtine"
showing 10 items of 10 documents
Pharmacological intervention in age-associated brain disorders by Flupirtine: Alzheimer’s and Prion diseases
1998
Alzheimer's disease, a major form of dementia in the elderly has become an increasingly important health problem in developed countries. In vitro studies on primary neurons demonstrate that Flupirtine (Katadolon) at a concentration of 1 microg/ml, significantly reduces the neurotoxic (apoptotic) effect displayed by A beta25-35, a segment of the amyloid beta-protein precursor the etiologic agent of Alzheimer's disease. Flupirtine, which has been in clinical use since 10 years ago, prevents the toxic effect of PrP, the presumed etiologic agent of the Creutzfeldt-Jakob disease as well as the excitatory amino acid glutamate on cortical neurons. Flupirtine displays a bimodal activity. Its strong…
Flupirtine protects both neuronal cells and lymphocytes against induced apoptosis in vitro: Implications for treatment of AIDS patients
1999
In the present study we demonstrate that flupirtine, an already clinically used, centrally acting, non-opiate analgesic agent, protects rat cortical neurons against HIV-gp120 induced apoptotic cell death. The drug was active at concentrations between 1 and 10 microg/ml. Furthermore we show inhibition of in vitro induced apoptosis in human blood mononuclear cells, using flupirtine. Induced apoptosis in peripheral blood mononuclear cells from healthy individuals and HIV-1 infected patients was reduced to approximately 50% after in vitro preincubation with flupirtine at concentrations between 0.1 and 10 microg/ml. The anti-apoptotic effect of flupirtine was restricted to CD3+ lymphocytes and i…
Antihyperalgesic and analgesic properties of the N-methyl-d-aspartate (NMDA) receptor antagonist neramexane in a human surrogate model of neurogenic …
2006
Abstract NMDA-receptors are a major target in the prevention and treatment of hyperalgesic pain states in neuropathic pain. However, previous studies revealed equivocal results depending on study design and efficacy parameters. We tested the analgesic (generalized reduction of generation and processing of nociceptive signalling) and anti-hyperalgesic (prevention of central sensitization) properties of the NMDA-receptor antagonist neramexane and the potassium channel opener flupirtine in the intradermal capsaicin injection model. Furthermore, we tested the effect on pain summation (wind up). Eighteen healthy subjects received either a single dose of neramexane (40 mg p.o.), flupirtine (100 m…
Novel approaches in diagnosis and therapy of Creutzfeldt-Jakob disease.
2000
The scrapie prion protein, PrP(Sc), as well as its peptide fragment, PrP106-126, are toxic on neuronal cells, resulting in cell death by an apoptotic, rather than necrotic mechanism. The apoptotic process of neuronal cells induced by prion protein supports diagnosis and offers potential targets for therapeutic intervention of the prion diseases. Among the cerebrospinal fluid (CSF) proteins, which may serve as markers of neuronal cell death associated with prion diseases, the 14-3-3 protein(s) turned out to be the most promising one. A new sensitive assay allows the detection of even small changes in the normally low levels of these proteins. In vitro, the toxic effects displayed by PrP(Sc) …
Protection of Flupirtine on β-Amyloid-Induced Apoptosis in Neuronal Cells In Vitro: Prevention of Amyloid-Induced Glutathione Depletion
2002
Effective drugs are not available to protect against beta-amyloid peptide (A beta)-induced neurotoxicity. Cortical neurons from rat embryos were treated with the toxic fragment A beta25-35 at 1 microM in the presence or absence of flupirtine, a triaminopyridine, successfully applied clinically as a nonopiate analgesic drug. Five days later 1 microM A beta25-35 caused reduction of cell viability to 31.1%. Preincubation of cells with flupirtine (1 or 5 microg/ml) resulted in a significant increase of the percentage of viable cells (74.6 and 65.4%, respectively). During incubation with A beta25-35 the neurons undergo apoptosis as determined by appearance of the characteristic stepladder-like D…
Neuroprotective effect of flupirtine in prion disease
2003
Apoptotic neuronal cell death is a hallmark of prion diseases. The apoptotic process in neuronal cells is thought to be caused by the scrapie prion protein, PrPSc, and can be experimentally induced by its peptide fragment, PrP106-126. This process is a target for potential drugs to combat prion disease or to ameliorate its symptoms. Flupirtine (Katadolon), a pyridine derivative that is in clinical use as a nonopioid analgesic, has a potent cytoprotective effect, at concentrations above 1 microg/mL, on neuronal cells treated with PrP(Sc) or PrP106-126. This drug acts as an N-methyl-D-aspartate (NMDA) antagonist, but does not bind to NMDA receptors. Flupirtine normalizes the level of intracel…
Flupirtine increases the levels of glutathione and Bcl-2 in hNT (human ) neurons: mode of action of the drug-mediated anti-apoptotic effect
1996
Flupirtine is a triaminopyridine analogue which has been successfully applied in clinics as a non-opiate analgesic drug. Previously we described that flupirtine acts like an N-methyl-D-aspartate (NMDA) receptor antagonist in neuronal cells both in vitro and in vivo. Here we show that flupirtine displays its anti-apoptotic effect also in hNT (human Ntera/D1) neurons. hNT neurons were induced to apoptosis applying glutamate (Glu; at concentrations > or = 1 mM) or NMDA (> or = 1 mM). During Glu/NMDA-mediated apoptosis the levels of the intracellular anti-apoptotic agents Bc1-2 and glutathione dropped by more than 50%. Flupirtine completely abolished this reduction of Bc1-2 and glutathione leve…
Effect of flupirtine on Bcl-2 and glutathione level in neuronal cells treated in vitro with the prion protein fragment (PrP106-126).
1997
Flupirtine, trade name Katadolon, is a centrally acting nonopioid analgesic that has recently been found to display cytoprotective activity in vitro and in vivo on neurons induced to undergo apoptosis. This report shows that the PrP106-126 fragment of the prion protein, which is the likely etiological agent for a series of encephalopathies, is toxic to cortical neurons in vitro. Simultaneously, PrP106-126 influences the molecular GSH content and the bcl-2 expression in neurons. Significant toxicity (32% reduction in cell viability) was observed at a concentration of 50 microM of the peptide after 9 days of incubation, while at higher concentrations toxicity increased to 70%. Neurotoxicity w…
The triaminopyridine flupirtine prevents cell death in rat cortical cells induced by N-methyl-D-aspartate and gp120 of HIV-1.
1994
Abstract Flupirtine, a triaminopyridine derivative, is a non-opiate centrally acting analgesic agent with muscle relaxant properties. Now we show that this drug displays a potent cytoprotective effect on neurons (rat cortical cells) treated with (i) the excitatory amino acid N-methyl- d -aspartate (NMDA) or (ii) with the human immunodeficiency virus type 1 (HIV-1) coat protein gp120. In the absence of the drug the two agents cause a >90% reduction of cell viability after a 18 h incubation. During this period the DNA in the cells undergoes fragmentation and shows a pattern which is typical for cell death. If the neurons were preincubated with flupirtine for 2 h and subsequently exposed to th…
Effect of flupirtine on cell death of human umbilical vein endothelial cells induced by reactive oxygen species.
1999
Abstract Flupirtine (KATADOLON®), known as a nonopiate centrally acting analgesic drug, was tested as to its potential to prevent apoptosis of human endothelial cells induced by reactive oxygen species (ROS). It was found that Flupirtine displayed no effect on viability and cell proliferation of human umbilical vein endothelial cells (HUVEC) up to a concentration of 10 μg/mL. Apoptosis, induced by ROS and generated by hypoxanthine/xanthine oxidase (EC 1.1.3.22) (HX/XOD) or t-butyl hydroperoxide, was reduced after preincubation with Flupirtine for 3 hr by 35% and 41%, respectively. The maximal cytoprotective effect against apoptosis was observed at a drug concentration of 1 to 3 μg/mL. Flow …