Targeting the prostaglandin E2 EP1 receptor and cyclooxygenase-2 in the amygdala kindling model in mice

Epilepsy Research
Sarah Verena FischbornHeidrun Potschka

Abstract

The prostaglandin E2 EP1 receptor as well as the inflammatory enzyme cyclooxygenase-2 have been suggested as targets for disease modulation, improvement of therapeutic response, and restoration of pharmacosensitivity in epilepsies. Translational development of respective add-on approaches requires careful analysis of putative effects on ictogenesis. Therefore we evaluated the impact of the EP1 receptor antagonist SC-51089, the EP1 receptor agonist misoprostol and the COX-2 inhibitors celecoxib and NS-398 in the mouse amygdala kindling model of temporal lobe epilepsy. Neither celecoxib nor NS-398 affected the generation, spread and termination of seizure activity. Whereas SC-51089 did not affect the seizure threshold, the highest dose (30mg/kg) significantly decreased the seizure severity when administered 60min before stimulation. Moreover, SC-51089 significantly prolonged seizure duration at the highest dose. The EP1 receptor agonist misoprostol exerted contrasting effects on seizure duration with a significant decrease in the duration of motor seizure activity. The data suggest that doses of COX-2 inhibitors and EP1 receptor antagonists which exert disease modulating or antiepileptic drug potentiating effects do not negativel...Continue Reading

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Citations

Apr 12, 2016·Trends in Pharmacological Sciences·Avijit DeyJianxiong Jiang
Nov 27, 2014·PloS One·Alexander V GlushakovSylvain Doré
Nov 2, 2019·Journal of Neuroinflammation·Chitra RawatRitushree Kukreti
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Aug 28, 2019·Progress in Neurobiology·Ying YuJianxiong Jiang
Nov 10, 2021·Molecular Biology Reports·Shubham VishwakarmaThakur Gurjeet Singh

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