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Titolo:
Metabotropic glutamate receptor subtypes as targets for neuroprotective drugs
Autore:
Bruno, V; Battaglia, G; Copani, A; DOnofrio, M; Di Iorio, P; De Blasi, A; Melchiorri, D; Flor, PJ; Nicoletti, F;
Indirizzi:
Univ Roma La Sapienza, Dept Human Physiol & Pharmacol, I-00185 Rome, ItalyUniv Roma La Sapienza Rome Italy I-00185 Pharmacol, I-00185 Rome, Italy INM Neuromed, Pozzilli, Italy INM Neuromed Pozzilli ItalyINM Neuromed, Pozzilli, Italy Univ Catania, Dept Pharmaceut Sci, Catania, Italy Univ Catania Catania Italy Catania, Dept Pharmaceut Sci, Catania, Italy Univ Chieti, Dept Biomed Sci, Chieti, Italy Univ Chieti Chieti ItalyUniv Chieti, Dept Biomed Sci, Chieti, Italy Novartis Pharma AG, Nervous Syst Res, Basel, Switzerland Novartis Pharma AG Basel Switzerland rvous Syst Res, Basel, Switzerland
Titolo Testata:
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
fascicolo: 9, volume: 21, anno: 2001,
pagine: 1013 - 1033
SICI:
0271-678X(200109)21:9<1013:MGRSAT>2.0.ZU;2-E
Fonte:
ISI
Lingua:
ENG
Soggetto:
GROWTH-FACTOR-BETA; CEREBELLAR GRANULE CELLS; EXCITOTOXIC NEURONAL DEATH; RAT HIPPOCAMPAL SLICES; CULTURED CORTICAL-NEURONS; ISCHEMIC BRAIN INJURY; AMINO-ACID RECEPTORS; PROTEIN-KINASE-C; GROUP-III MGLUR; GROUP-I MGLURS;
Keywords:
mGlu receptors; neuroprotection; subtype-selective ligands;
Tipo documento:
Review
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
206
Recensione:
Indirizzi per estratti:
Indirizzo: Nicoletti, F Univ Roma La Sapienza, Dept Human Physiol & Pharmacol, Piazzale Aldo Moro 5, I-00185 Rome, Italy Univ Roma La Sapienza Piazzale Aldo Moro 5 Rome Italy I-00185
Citazione:
V. Bruno et al., "Metabotropic glutamate receptor subtypes as targets for neuroprotective drugs", J CEREBR B, 21(9), 2001, pp. 1013-1033

Abstract

Metabotropic glutamate (mGlu) receptors have been considered as potential targets for neuroprotective drugs. but the lack of specific drugs has limited the development of neuroprotective strategies in experimental models of acute or chronic central nervous system (CNS) disorders. The advent of potent and centrally available subtype-selective ligands has overcome this limitation, leading to an extensive investigation of the role of mGlu receptor subtypes in neurodegeneration during the last 2 years. Examples of these drugs are the noncompetitive mGlu1 receptor antagonists, CPCCOEt and BAY-36-7620; the noncompetitive mGlu5 receptor antagonists, 2-methyl-6-(phenylethynyl)pyridine, SIB-1893, and SIB-1757; and the potent mGlu2/3 receptor agonists, LY354740 and LY379268. Pharmacologic blockade of mGlu I or mGlu5 receptors or pharmacologic activation of mGlu2/3 or mGlu4/7/8 receptors produces neuroprotection in a variety of in vitro or in vivo models. MGlu1 receptor antagonists are promising drugs for the treatment of brain ischemia or for the prophylaxis of neuronal damage induced by synaptic hyperactivity. MGlu5receptor antagonists may limit neuronal damage induced by a hyperactivity of N-methyl-d-aspartate (NMDA) receptors, because mGlu5 and NMDA receptors are physically and functionally connected in neuronal membranes. A series of observations suggest a potential application of mGlu5 receptor antagonists in chronic neurodegenerative disorders, such as amyotrophic lateral sclerosis and Alzheimer disease. MGlu2/3 receptor agonists inhibit glutamate release, but also promote the synthesis and release of neurotrophic factors inastrocytes. These drugs may therefore have a broad application as neuroprotective agents in a variety of CNS disorders. Finally, mGlu4/7/8 receptor agonists potently inhibit glutamate release and have a potential applicationin seizure disorders. The advantage of all these drugs with respect to NMDA or AMPA receptor agonists derives from the evidence that mGlu receptors do not "mediate," but rather "modulate" excitatory synaptic transmission. Therefore. it can be expected that mGlu receptor ligands are devoid of the undesirable effects resulting from the inhibition of excitatory synaptic transmission, such as sedation or an impairment of learning and memory.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 04/04/20 alle ore 08:45:20