Linked Life Data

15857300

Source:http://linkedlifedata.com/resource/pubmed/id/15857300

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2005-4-28
pubmed:abstractText
Signal transduction via ionotropic glutamate receptors is found in many life forms, from protozoa to mammals. Glutamate is the main excitatory neurotransmitter in the mammalian CNS, were fast postsynaptic depolarisation is induced by the activation of AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) receptors. In addition to their important physiological role, excessive AMPA receptor stimulation is also a hallmark of excitotoxicity-related diseases, like ischaemic stroke. Conversely, AMPA receptor inhibitors were proposed to be useful neuroprotective drugs. First generation AMPA receptor blockers were competitive antagonists, like NBQX, which showed robust neuroprotection in a variety of disease-related animal models. Its clinical use, however, was restricted by the very low solubility, inducing kidney precipitaton in vivo. Second generation competitive antagonists are available, which do not possess this property. None of those, however, up to now is in clinical use. Competitive AMPA receptor antagonists are not the first choice for neuroprotective drugs, since due to receptor kinetics they preferently suppress the physiological relevant component of the postsynaptic glutamate response. Non-competitive blockers, like 2,3-benzodiazepines or the novel neuroprotectant BIIR 561 should be suited better for the treatment of stroke. The latter compound is also described as blocker of voltage-gated sodium channels. Targetting more than one mechanism in the excitotoxicity cascade might be a fruitful approach for the development of neuroprotective drugs.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
1568-007X
pubmed:author
pubmed:issnType
Print
pubmed:volume
4
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
153-9
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed:year
2005
pubmed:articleTitle
AMPA receptor antagonists for the treatment of stroke.
pubmed:affiliation
CNS Research, Boehringer Ingelheim Pharma GmbH & Co KG, Birkendorfer Strasse, D-88397 Biberach, Germany. thomas.weiser@bc.boehringer-ingelheim.com
pubmed:publicationType
Journal Article, Review