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 language | English |
|---|---|
| Pages (from-to) | 52-57 |
| Number of pages | 6 |
| Journal | Epilepsy and Behavior |
| Volume | 16 |
| Issue number | 1 |
| DOIs | |
| State | Published - Sep 2009 |
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All Science Journal Classification (ASJC) codes
- Clinical Neurology
- Behavioral Neuroscience
- Neurology
Cite this
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 journal › Article
}
TY - JOUR
T1 - Anticonvulsant effects of the selective melatonin receptor agonist ramelteon
AU - Simeone, Kristina A.
AU - Mazarati, Andrey
AU - Sefidvash-Hockley, Sepideh
AU - Shin, Don
AU - Wilke, Julianne
AU - Milligan, Heather
AU - Sankar, Raman
AU - Rho, Jong M.
AU - Maganti, Rama
PY - 2009/9
Y1 - 2009/9
N2 - 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.
AB - 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.
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U2 - 10.1016/j.yebeh.2009.07.022
DO - 10.1016/j.yebeh.2009.07.022
M3 - Article
VL - 16
SP - 52
EP - 57
JO - Epilepsy and Behavior
JF - Epilepsy and Behavior
SN - 1525-5050
IS - 1
ER -