Anticonvulsant effects of the selective melatonin receptor agonist ramelteon

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

Research output: Contribution to journalArticle

38 Citations (Scopus)

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

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Melatonin Receptors
Anticonvulsants
Periodicity
Epilepsy
Seizures
Actigraphy
Melatonin
ramelteon
Electroencephalography
Theoretical Models
Animal Models
Hormones

All Science Journal Classification (ASJC) codes

  • Clinical Neurology
  • Behavioral Neuroscience
  • Neurology

Cite this

Simeone, K. A., Mazarati, A., Sefidvash-Hockley, S., Shin, D., Wilke, J., Milligan, H., ... 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

Anticonvulsant effects of the selective melatonin receptor agonist ramelteon. / Simeone, Kristina A.; Mazarati, Andrey; Sefidvash-Hockley, Sepideh; Shin, Don; Wilke, Julianne; Milligan, Heather; Sankar, Raman; Rho, Jong M.; Maganti, Rama.

In: Epilepsy and Behavior, Vol. 16, No. 1, 09.2009, p. 52-57.

Research output: Contribution to journalArticle

Simeone, KA, Mazarati, A, Sefidvash-Hockley, S, Shin, D, Wilke, J, Milligan, H, Sankar, R, Rho, JM & Maganti, R 2009, 'Anticonvulsant effects of the selective melatonin receptor agonist ramelteon', Epilepsy and Behavior, vol. 16, no. 1, pp. 52-57. https://doi.org/10.1016/j.yebeh.2009.07.022
Simeone, Kristina A. ; Mazarati, Andrey ; Sefidvash-Hockley, Sepideh ; Shin, Don ; Wilke, Julianne ; Milligan, Heather ; Sankar, Raman ; Rho, Jong M. ; Maganti, Rama. / Anticonvulsant effects of the selective melatonin receptor agonist ramelteon. In: Epilepsy and Behavior. 2009 ; Vol. 16, No. 1. pp. 52-57.
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