Linked Life Data

16563443

Source:http://linkedlifedata.com/resource/pubmed/id/16563443

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
2006-6-5
pubmed:abstractText
Modulation of metabotropic glutamate (mGlu) receptors represents an interesting new approach for the treatment of a range of neurological and psychiatric disorders. Several lines of evidence suggest that functional blockade of group I (mGlu1 and mGlu5) receptors may be beneficial for treatment of epileptic seizures. This study was conducted to investigate whether mGlu1 or mGlu5 receptor antagonists have the potential to block partial or secondarily generalized seizures as occurring in partial epilepsy, the most common and difficult-to-treat type of epilepsy in patients. For this purpose, we systemically administered novel highly selective and brain penetrable group I mGlu receptor antagonists, i.e., the mGlu1 receptor antagonist EMQMCM [3-ethyl-2-methyl-quinolin-6-yl-(4-methoxy-cyclohexyl)-methanone methanesulfonate] and the mGlu5 receptor antagonist MTEP ([(2-methyl-1,3-thiazol-4-yl) ethynyl] pyridine), at doses appropriate for mGlu1 or mGlu5 receptor-mediated effects in rodent models of partial seizures. Two models were used: the 6-Hz electroshock model of partial seizures in mice and the amygdala-kindling model in rats. Clinically established antiepileptic drugs were included in the experiments for comparison. Antiepileptic drugs exerted significant anticonvulsant effects in both models, while EMQMCM and MTEP were ineffective in this regard, although both compounds were administered up to doses associated with essentially full receptor occupancy and with typical mGlu receptor-mediated effects in rodent models of anxiety or pain. Brain microdialysis for determining extracellular levels of MTEP following i.p. administration in rats substantiated that effective brain concentrations were reached at times of our experiments in seizure models. The present results do not support a significant anticonvulsant potential of group I mGlu receptor antagonists in rodent models of difficult-to-treat partial epilepsy.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0028-3908
pubmed:author
pubmed:issnType
Print
pubmed:volume
50
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1006-15
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:16563443-Animals, pubmed-meshheading:16563443-Anticonvulsants, pubmed-meshheading:16563443-Behavior, Animal, pubmed-meshheading:16563443-Differential Threshold, pubmed-meshheading:16563443-Disease Models, Animal, pubmed-meshheading:16563443-Dose-Response Relationship, Drug, pubmed-meshheading:16563443-Electroshock, pubmed-meshheading:16563443-Epilepsies, Partial, pubmed-meshheading:16563443-Excitatory Amino Acid Antagonists, pubmed-meshheading:16563443-Male, pubmed-meshheading:16563443-Mice, pubmed-meshheading:16563443-Microdialysis, pubmed-meshheading:16563443-Pyridines, pubmed-meshheading:16563443-Rats, pubmed-meshheading:16563443-Rats, Sprague-Dawley, pubmed-meshheading:16563443-Receptors, Metabotropic Glutamate, pubmed-meshheading:16563443-Statistics, Nonparametric, pubmed-meshheading:16563443-Thiazoles
pubmed:year
2006
pubmed:articleTitle
mGlu1 and mGlu5 receptor antagonists lack anticonvulsant efficacy in rodent models of difficult-to-treat partial epilepsy.
pubmed:affiliation
Department of Pharmacology, Toxicology and Pharmacy, University of Veterinary Medicine, Bünteweg 17, D-30559 Hannover, Germany. wolfgang.loescher@tiho-hannover.de
pubmed:publicationType
Journal Article, Comparative Study