کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
3050560 1185956 2009 6 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Anticonvulsant effects of the selective melatonin receptor agonist ramelteon
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی علوم اعصاب رفتاری
پیش نمایش صفحه اول مقاله
Anticonvulsant effects of the selective melatonin receptor agonist ramelteon
چکیده انگلیسی

ObjectiveThe endogenous hormone melatonin has previously been shown to exert anticonvulsant effects in a variety of experimental models. Accordingly, we asked whether ramelteon, a synthetic and selective melatonin receptor agonist, might also possess anticonvulsant and/or antiepileptogenic properties.MethodsThe effects of ramelteon (30 or 100 mg/kg intraperitoneally twice daily for 5 days) were evaluated in two animal models of epilepsy. In the rat rapid kindling model, baseline hippocampal afterdischarge properties, kindling progression, and hippocampal excitability in kindled animals were measured. Anti-ictogenic efficacy was assessed after acute administration in untreated kindled rats. In the spontaneously epileptic Kcna1-null mouse model, we determined seizure frequency and periodicity using continuous video/EEG monitoring over 72 hours. Further, circadian rest–activity rhythms in ramelteon-treated animals were studied with actigraphy.ResultsIn kindled animals, ramelteon reversed kindling-induced hippocampal excitability; however, it did not modify baseline afterdischarge properties, the progression and establishment of the kindled state in the rapid kindling model. However, in Kcna1-null mice, ramelteon (200 mg/kg/day) significantly attenuated seizure periodicity and frequency and improved circadian rest–activity rhythms compared with control animals.ConclusionsThe selective melatonin receptor agonist ramelteon possesses anticonvulsant properties in a chronic epilepsy model. Our findings provide further support for melatonin receptors being potential novel targets for anticonvulsant drug development.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Epilepsy & Behavior - Volume 16, Issue 1, September 2009, Pages 52–57
نویسندگان
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