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Titolo:
Phosphonate quinoxalinedione AMPA antagonists
Autore:
Turski, L; Schneider, HH; Neuhaus, R; McDonald, F; Jones, GH; Lofberg, B; Schweinfurth, H; Huth, A; Kruger, M; Ottow, E;
Indirizzi:
Schering AG, Res Labs, D-13342 Berlin, Germany Schering AG Berlin Germany D-13342 AG, Res Labs, D-13342 Berlin, Germany
Titolo Testata:
RESTORATIVE NEUROLOGY AND NEUROSCIENCE
fascicolo: 1, volume: 17, anno: 2000,
pagine: 45 - 59
SICI:
0922-6028(2000)17:1<45:PQAA>2.0.ZU;2-8
Fonte:
ISI
Lingua:
ENG
Soggetto:
EXCITATORY AMINO-ACIDS; RAT CORTICAL MEMBRANES; D-ASPARTATE ANTAGONIST; ACUTE ISCHEMIC STROKE; NON-NMDA RECEPTORS; FOCAL ISCHEMIA; CEREBRAL-ISCHEMIA; QUISQUALATE RECEPTORS; FOREBRAIN ISCHEMIA; GLOBAL-ISCHEMIA;
Keywords:
glutamate antagonists; anxiety; analgesia; muscle tone; seizures; stroke; traumatic brain injury; neuroprotection;
Tipo documento:
Review
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
69
Recensione:
Indirizzi per estratti:
Indirizzo: Turski, L Solvay Pharmaceut, Res Labs, CJ van Houtenlaan 36, NL-1381 CP Weesp, Netherlands Solvay Pharmaceut CJ van Houtenlaan 36 Weesp Netherlands NL-1381 CP
Citazione:
L. Turski et al., "Phosphonate quinoxalinedione AMPA antagonists", REST NEUROL, 17(1), 2000, pp. 45-59

Abstract

In the Western world, over 350,000 deaths and $30 billion in medical costsare attributed annually to stroke. Head and spinal cord trauma cause an estimated 250,000 deaths annually and result in medical costs of $15 billion. Although stroke and head/spinal cord trauma are leading causes of disability and death in humans, no adequate neuroprotective treatment is available. Glutamate antagonists derived from the quinoxalinedione scaffold are as drug candidates for neuroprotection in stroke and trauma. Quinoxalinedione derivatives such as 2,3-dihydroxy-6-nitro-7-sulfamoylbenzo(f)quinoxaline and 6-(1H-imidazol-1-yl)-7-nitro-2,3-(1H,4H)-quinoxalinedione failed clinical trials because of insolubility and resulting nephrotoxicity. Introduction ofa phosphonate group into the quinoxalinedione skeleton improves solubilityand leaves potency for the alpha -amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptor unchanged. Phosphonate quinoxalinedione derivatives ZK202000 and ZK200775 protected rodent brain against sequelae of permanent occlusion of the middle cerebral artery and head trauma. No major deleterious effects on motor coordination, cardiovascular, or respiratory systems were detected in doses required for neuroprotection. No psychotomimetic and no neurotoxic side effects, typical for N-methyl-D-aspartate antagonists, were observed following treatment with phosphonate quinoxalinediones.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 05/07/20 alle ore 22:45:43