Anticonvulsant effects of the selective melatonin receptor agonist ramelteon

Kristina Fenoglio-Simeone, Andrey Mazarati, Sepideh Sefidvash-Hockley, Don Shin, Julianne Wilke, Heather Milligan, Raman Sankar, Jong M. Rho, Rama Maganti

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Abstract

Objective: The 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. Methods: The 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. Results: In 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. Conclusions: The 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.

Original languageEnglish (US)
Pages (from-to)52-57
Number of pages6
JournalEpilepsy and Behavior
Volume16
Issue number1
DOIs
StatePublished - Sep 1 2009

All Science Journal Classification (ASJC) codes

  • Neurology
  • Clinical Neurology
  • Behavioral Neuroscience

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    Fenoglio-Simeone, K., Mazarati, A., Sefidvash-Hockley, S., Shin, D., Wilke, J., Milligan, H., Sankar, R., Rho, J. M., & Maganti, R. (2009). Anticonvulsant effects of the selective melatonin receptor agonist ramelteon. Epilepsy and Behavior, 16(1), 52-57. https://doi.org/10.1016/j.yebeh.2009.07.022