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Titolo:
Topiramate blocks kainate-evoked cobalt influx into cultured neurons
Autore:
Skradski, S; White, HS;
Indirizzi:
Univ Utah, Coll Pharm, Dept Pharmacol & Toxicol, Anticonvulsant Screening Project, Salt Lake City, UT 84112 USA Univ Utah Salt Lake City UT USA 84112 oject, Salt Lake City, UT 84112 USA
Titolo Testata:
EPILEPSIA
, volume: 41, anno: 2000, supplemento:, 1
pagine: S45 - S47
SICI:
0013-9580(2000)41:<S45:TBKCII>2.0.ZU;2-1
Fonte:
ISI
Lingua:
ENG
Soggetto:
REFRACTORY PARTIAL EPILEPSY; PLACEBO-CONTROLLED TRIAL; DOSE-RANGING TRIAL; DOUBLE-BLIND; RECEPTOR ANTAGONISTS; DAILY DOSAGES; NBQX; ANTICONVULSANT; GYKI-52466; SEIZURES;
Keywords:
topiramate; kainate; antiepileptic drugs; epilepsy;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
19
Recensione:
Indirizzi per estratti:
Indirizzo: White, HS Univ Utah, Coll Pharm, Dept Pharmacol & Toxicol, Anticonvulsant Screening Project, Salt Lake City, UT 84112 USA Univ Utah Salt Lake City UT USA 84112 t Lake City, UT 84112 USA
Citazione:
S. Skradski e H.S. White, "Topiramate blocks kainate-evoked cobalt influx into cultured neurons", EPILEPSIA, 41, 2000, pp. S45-S47

Abstract

Purpose: This study evaluated topiramate (TPM) antagonism of glutamate receptors activated by kainate. Methods: The ability of TPM (3-30 mu M) to attenuate kainate (300 mu M)-activated cobalt (Co2+) flux through nonselective cation channels permeable to Co2+, Mn2+, and Ca2+ into cultured cerebellar granule neurons [9-14 days in vitro (div)] was investigated. Results were compared with those obtainedwith the non-N-methyl-D-aspartate (non-NMDA) antagonist 6,7-dinitroquinoxalone-2,3-dione (DNQX) (10 mu M). Results: Topiramate produced a concentration- and time-dependent inhibition of Co2+ uptake into cerebellar granule cells cultured 9-11 div. Inhibition was evident at 10 mu M, and complete inhibition was observed at 30 mu M Maximal inhibition of Co2+ uptake required pretreatment with TPM for greaterthan or equal to 30 minutes before stimulation by kainate. The effect of 30 mu M TPM on Co2+ uptake was similar to that of 10 mu M DNQX. However, TPM, unlike DNQX, did not affect kainate-evoked Co2+ uptake into older neurons(i.e., 13-14 div). Conclusions: These results provide additional support for an antagonistic effect of TPM on some types of alpha-amino-3-hydroxy-5-methylisoxazole-4-proprionic acid (AMPA) and/or kainate receptors, and specifically suggest that TPM interacts with a Ca2+-permeable non-NMDA receptor that is developmentally regulated. This observation may provide insight into the molecular biology underlying the pathophysiology of seizure disorders and antiepileptic drug resistance.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 01/04/20 alle ore 20:50:28