Search results for "glutamate receptor"

Selected peptides targeted to the NMDA receptor channel protect neurons from excitotoxic death

1998

Excitotoxic neuronal death, associated with neurodegeneration and stroke, is triggered primarily by massive Ca2+ influx arising from overactivation of glutamate receptor channels of the N-methyl-D-aspartate (NMDA) subtype. To search for channel blockers, synthetic combinatorial libraries were assayed for block of agonist-evoked currents by the human NR1-NR2A NMDA receptor subunits expressed in amphibian oocytes. A set of arginine-rich hexapeptides selectively blocked the NMDA receptor channel with IC50 approximately 100 nM, a potency similar to clinically tolerated blockers such as memantine, and only marginally blocked on non-NMDA glutamate receptors. These peptides prevent neuronal cell d…

Perampanel and Visuospatial Skills in Children With Epilepsy

2021

Introduction: Perampanel (PER) is a non-competitive AMPA glutamate receptor antagonist approved for focal and generalized seizures as add-on therapy. PER does not seem to negatively affect the cognitive profile in children and adolescents, but its influence on visuospatial abilities is still to be assessed. The aim of our study was to assess visuospatial skills through a standardized neuropsychological evaluation in adolescents taking PER for 12 months.Methods: Our sample included 46 adolescents aged 12–18 years with focal and generalized drug-resistant epilepsy already in therapy with one or two antiseizure medications. Changes in visuospatial perception and memory were assessed by the Rey…

Preclinical progress with CHF2819, a novel orally active acetylcholinesterase inhibitor

2002

(-)-(3aS,8aS,1S)-1,2,3,3a,8,8a-hexahydro-1,3a,8-trimethylpyrrolo[2,3-b]indol-5-ol-2′-ethylphenylcarbamate N-oxide hydrochloride (CHF2819) is a novel, orally active acetylcholinesterase inhibitor (AChEI) for Alzheimer's disease (AD). CHF2819 appears as a selective inhibitor of AChE, being 115 times more potent against this enzyme than butyrylcholinesterase (BuChE). Moreover, CHF2819 appears more selective for inhibiting central (brain) than peripheral (heart) AChE. In vivo studies show that CHF2819 significantly increases acetylcholine (ACh) levels in young adult rat hippocampus in a dose-dependent manner. Moreover, aged animals exhibit a marked increase in hippocampal concentrations of this…

CHF2819: Pharmacological profile of a novel acetylcholinesterase inhibitor

2002

CHF2819 is a novel orally active acetylcholinesterase inhibitor (AChEI) developed for the treatment of Alzheimer's disease (AD). CHF2819 is a selective inhibitor of AChE, it is 115 times more potent against this enzyme than against butyrylcholinesterase (BuChE). Moreover, CHF2819 is more selective for inhibition of central (brain) AChE than peripheral (heart) AChE. In vivo CHF2819, 0.5, 1.5, and 4.5 mg/kg p.o., significantly and in dose-dependent manner increased acetylcholine (ACh) levels in hippocampus of young adult rats. Moreover, aging animals, with lower basal ACh levels than young adult rats, also exhibit a marked increase in hippocampal levels of this neurotransmitter after administ…

Activation of mGlu3 Receptors Stimulates the Production of GDNF in Striatal Neurons

2009

Metabotropic glutamate (mGlu) receptors have been considered potential targets for the therapy of experimental parkinsonism. One hypothetical advantage associated with the use of mGlu receptor ligands is the lack of the adverse effects typically induced by ionotropic glutamate receptor antagonists, such as sedation, ataxia, and severe learning impairment. Low doses of the mGlu2/3 metabotropic glutamate receptor agonist, LY379268 (0.25-3 mg/kg, i.p.) increased glial cell line-derived neurotrophic factor (GDNF) mRNA and protein levels in the mouse brain, as assessed by in situ hybridization, real-time PCR, immunoblotting, and immunohistochemistry. This increase was prominent in the striatum, …

Anesthetics and Cerebral Protection in Patients Undergoing Carotid Endarterectomy

2015

EREBRAL ISCHEMIA/HYPOXIA may occur in a vari-ety of perioperative circumstances. The main pathophy-siologic aspects involved in cerebral ischemia/reperfusion arecaused by adenosine triphosphate (ATP) consumption, theexcitotoxic actions of glutamate, changes in ionic homeostasis,and formation of free radicals (Fig 1). Outcomes from suchevents range from subclinical neurocognitive deficits to cata-strophic neurologic morbidity or death.

Speciation of dimethyltin(IV) – and trimethyltin(IV) – carbocysteinate and – glutamate systems in aqueous media

2008

The formation of complex species in the dimethyltin(IV) and trimethyltin(IV)-carboxymethyl-L-cysteinate (carbocysteinate) systems in NaClaq, at different ionic strengths, and in a multicomponent Na+, K+, Ca2+, Mg2+, Cl- and SO42- medium representative of the seawater major composition, is discussed. Experimental results give evidence for the formation of the following species (L¼carbocysteinate): [(CH3)2Sn(L)]0, [(CH3)2Sn(HL)]+, [(CH3)2Sn(OH)(L)]-, [(CH3)2Sn(OH)2(L)]2- in the DMT–CCYS system, and [(CH3)3Sn(HL)]0, [(CH3)3Sn(L)]- and [(CH3)3Sn(OH)(L)]2- in the TMT-CCYS system. The ionic strength dependence of formation constants was taken into account by an extended Debye Huckel type equation…

Metabotropic glutamate receptors activate phospholipase D in astrocytes through a protein kinase C-dependent and Rho-independent pathway.

2003

Metabotropic glutamate receptors (mGluRs) are G protein-coupled receptors that mediate phospholipase D (PLD) activation in brain, but the mechanism underlying this response remains unclear. Here we used primary cultures of astrocytes as a cell model to explore the mechanism that links mGluRs to PLD. Glutamate activated both phospholipase C (PLC) and PLD with equal potency and this effect was mimicked by L-cysteinesulfinic acid, a putative neurotransmitter previously shown to activate mGluRs coupled to PLD, but not PLC, in adult brain. PLD activation by glutamate was dependent on Ca(2+) mobilization and fully blocked by both protein kinase C (PKC) inhibitors and PKC down-regulation, suggesti…

Effect of ligand-binding on protein function

2014