FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2044090862> ?p ?o ?g. }

• W2044090862 endingPage "250" @default.
• W2044090862 startingPage "249" @default.
• W2044090862 abstract "Aberrant excitatory neurotransmission is a prominent pathological component in many neurological and psychiatric diseases. Not surprisingly, the proteins that mediate the majority of excitatory signaling, ionotropic glutamate receptors (iGluRs), represent tempting targets for drug development efforts. This potential remains largely unrealized, however, despite a wealth of promising preclinical data. Here I discuss briefly the new applications and candidate drugs acting on the AMPA and kainate subtypes of iGluRs that suggest that a renaissance might be underway.AMPA and kainate receptors sub-serve different roles in the brain. AMPA receptors mediate the majority of fast excitatory neurotransmission and are critical cellular constituents of learning and memory processes. Over-activation of AMPA receptors, however, can be damaging to the nervous system, producing convulsions or neuronal death. Kainate receptors play more modulatory roles, fine-tuning the balance between neuronal excitation and inhibition.Positive AMPA receptor modulators strengthen excitatory transmission, enhance synaptic plasticity, and preclinical and preliminary clinical research suggested efficacy as cognition enhancers (Lynch, 2006; O’Neill and Dix, 2007). The first potentiator tested in large clinical trials was CX516 (Cortex Pharmaceuticals), which did not show efficacy in a variety of pathologies (eg Berry-Kravis et al, 2006). In contrast, a second-generation ampakine, CX717, normalized behaviors associated with attention deficit hyperactivity disorder (ADHD). Further testing of CX717 for ADHD was not approved by the US Food and Drug Administration due to toxicological concerns, although approval was granted to continue trials of CX717 in Alzheimer’s disease. The outcome of this project is uncertain, however, given that a chemically distinct potentiator, LY415395 (Eli Lilly), failed to improve cognitive performance in an Alzheimer’s disease trial (Chappell et al, 2007). Recently, compelling preclinical data prompted initiation of two Phase II trials in Germany to determine if CX717 reverses or prevents respiratory depression during opiate analgesia. These appear to be the only ongoing studies of efficacy for positive AMPA receptor modulators in humans, as clinical studies for similar molecules have been suspended (Schering-Plough) or the results remain undisclosed (Servier, GlaxoSmithKline).Noncompetitive inhibitors of AMPA receptors, such as talampanel (Teva Pharmaceuticals) and perampanel (Eisai Medical Research), reduce over-excitation and potentially slow neuro-degeneration. These drugs were efficacious as adjunct therapies for refractory partial complex seizures (Howes and Bell, 2007); perampanel also alleviated diabetic and post-herpetic neuropathic pain and will be further tested for these indications. Results released from an in-progress study suggested that talampanel decreased mortality from glioblastoma, and an examination of its efficacy in amyotrophic lateral sclerosis is planned. Perampanel was not effective as an add-on therapy to levodopa in Parkinson’s disease, however, and this program was terminated by Eisai.Preclinical data suggest that kainate receptors represent an untapped and attractive target for drug development. A nonselective AMPA/kainate receptor inhibitor, tezampanel (NGX424; Torrey Pines Pharmaceutics), reduced both migraine pain and other symptoms in a recent Phase II trial. This clinical efficacy is likely attributable to inhibition of kainate receptors, based on preclinical evidence with more selective antagonists developed by Eli Lilly. A chemically distinct AMPA/kainate receptor antagonist, NS1209 (NeuroSearch A/S), also alleviated refractory status epilepticus and neuro-pathic pain in small Phase II studies, but further research into this molecule was suspended. The apparent success of the first representatives of this new class of drugs provides a strong impetus for further development and clinical testing.It is evident from this overview that there is reason for both optimism and healthy skepticism regarding the clinical prospects of drugs targeting AMPA and kainate receptors. Cusp of a renaissance or a false dawn? Perhaps a Magic 8-Ball offers the best advice for would-be prognosticators: ‘Ask again later.’" @default.
• W2044090862 created "2016-06-24" @default.
• W2044090862 creator A5023213448 @default.
• W2044090862 date "2008-12-12" @default.
• W2044090862 modified "2023-09-23" @default.
• W2044090862 title "Targeting AMPA and kainate receptors in neurological disease: therapies on the horizon?" @default.
• W2044090862 cites W1974716768 @default.
• W2044090862 cites W2040009554 @default.
• W2044090862 cites W2058128885 @default.
• W2044090862 cites W3190168223 @default.
• W2044090862 doi "https://doi.org/10.1038/npp.2008.158" @default.
• W2044090862 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/2715329" @default.
• W2044090862 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/19079074" @default.
• W2044090862 hasPublicationYear "2008" @default.
• W2044090862 type Work @default.
• W2044090862 sameAs 2044090862 @default.
• W2044090862 citedByCount "39" @default.
• W2044090862 countsByYear W20440908622012 @default.
• W2044090862 countsByYear W20440908622013 @default.
• W2044090862 countsByYear W20440908622014 @default.
• W2044090862 countsByYear W20440908622015 @default.
• W2044090862 countsByYear W20440908622016 @default.
• W2044090862 countsByYear W20440908622017 @default.
• W2044090862 countsByYear W20440908622018 @default.
• W2044090862 countsByYear W20440908622019 @default.
• W2044090862 countsByYear W20440908622020 @default.
• W2044090862 countsByYear W20440908622021 @default.
• W2044090862 countsByYear W20440908622023 @default.
• W2044090862 crossrefType "journal-article" @default.
• W2044090862 hasAuthorship W2044090862A5023213448 @default.
• W2044090862 hasBestOaLocation W20440908621 @default.
• W2044090862 hasConcept C126322002 @default.
• W2044090862 hasConcept C15744967 @default.
• W2044090862 hasConcept C160268369 @default.
• W2044090862 hasConcept C169760540 @default.
• W2044090862 hasConcept C170493617 @default.
• W2044090862 hasConcept C189184402 @default.
• W2044090862 hasConcept C61174792 @default.
• W2044090862 hasConcept C71924100 @default.
• W2044090862 hasConceptScore W2044090862C126322002 @default.
• W2044090862 hasConceptScore W2044090862C15744967 @default.
• W2044090862 hasConceptScore W2044090862C160268369 @default.
• W2044090862 hasConceptScore W2044090862C169760540 @default.
• W2044090862 hasConceptScore W2044090862C170493617 @default.
• W2044090862 hasConceptScore W2044090862C189184402 @default.
• W2044090862 hasConceptScore W2044090862C61174792 @default.
• W2044090862 hasConceptScore W2044090862C71924100 @default.
• W2044090862 hasIssue "1" @default.
• W2044090862 hasLocation W20440908621 @default.
• W2044090862 hasLocation W20440908622 @default.
• W2044090862 hasLocation W20440908623 @default.
• W2044090862 hasLocation W20440908624 @default.
• W2044090862 hasOpenAccess W2044090862 @default.
• W2044090862 hasPrimaryLocation W20440908621 @default.
• W2044090862 hasRelatedWork W1972566831 @default.
• W2044090862 hasRelatedWork W2000626734 @default.
• W2044090862 hasRelatedWork W2009042957 @default.
• W2044090862 hasRelatedWork W2009730131 @default.
• W2044090862 hasRelatedWork W2025676835 @default.
• W2044090862 hasRelatedWork W2062051253 @default.
• W2044090862 hasRelatedWork W2063461600 @default.
• W2044090862 hasRelatedWork W2102027630 @default.
• W2044090862 hasRelatedWork W2170785039 @default.
• W2044090862 hasRelatedWork W2753475615 @default.
• W2044090862 hasVolume "34" @default.
• W2044090862 isParatext "false" @default.
• W2044090862 isRetracted "false" @default.
• W2044090862 magId "2044090862" @default.
• W2044090862 workType "article" @default.