The anticonvulsant effect of the broad spectrum anticonvulsant loreclezole may be mediated in part by serotonin in rats: a microdialysis study.
Loreclezole is an experimental anticonvulsant drug. We found previously that several established anticonvulsants increase extracellular serotonin as measured by microdialysis. We have concluded that the increase in extracellular serotonin and the anticonvulsant effect produced by these anticonvulsant drugs are related in a cause and effect manner. To determine if anticonvulsant doses of loreclezole increase extracellular serotonin, we determined anticonvulsant dose-response relationships in genetically epilepsy-prone rats (GEPRs). Then, we administered ED99 doses of loreclezole to GEPRs and determined the effect on extracellular serotonin as measured by microdialysis in the striatum. We conclude that loreclezole produces a dose-related anticonvulsant effect in GEPRs and that anticonvulsant doses of loreclezole increase extracellular serotonin in these animals.
Dailey
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JW
Department of Basic Sciences, University of Illinois College of Medicine at Peoria 61656.
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D000161:Acoustic Stimulation; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004827:Epilepsy / Q000235:genetics / Q000503:physiopathology*; D020022:Genetic Predisposition to Disease; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D017551:Microdialysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000502:physiology*; D014230:Triazoles / Q000494:pharmacology*
D000927:Anticonvulsants; D014230:Triazoles; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; C066440:loreclezole