Anticonvulsant effects reported with 5-HT3R ligands

CategoryCompound, Dose, Route of AdministrationStudy DesignEffectsProposed MechanismsReference
5-HT3R agonistsm-CPBG (5 and 10 mg/kg, i.p.)PTZ-induced seizure in micePotentiates the anticonvulsant effect of low doses of citalopram5-HT3R activation increases firing of interneurons and subsequent GABA releasePayandemehr et al., 2012
m-CPBG (1 mg/kg, i.p.)PTZ-induced seizure in micePotentiates the anticonvulsant effect of genistein5-HT3R is involved in the anticonvulsant effect of genisteinAmiri Gheshlaghi et al., 2017
SR 57227 (20–40 mg/kg, i.p.)PTZ-induced seizure in miceAnticonvulsant; prolongs seizure latency, reduces seizure score and mortality5-HT3R activation may result in GABA release in the hippocampusLi et al., 2014
SR57227 (10 mg/kg, i.p.)PTZ-induced seizure threshold in miceIncreases seizure threshold5-HT3 activation may result in GABA releaseGholipour et al., 2010
5-HT3R antagonistsHBK-15 (20, 30, and 40 mg/kg, i.p.)aMaximal electroshock-induced seizure in miceIncreases the threshold for tonic seizuresCombined antagonistic action at 5-HT1A/5-HT3/5-HT7 receptors and voltage-dependent sodium channelsPytka et al., 2017
Ondansetron (0.1, 0.5, and 1 mg/kg per day for 20 days, i.p.)PTZ-induced kindling in miceReduction in seizure severity and associated memory deficit in a dose-dependent mannerReduction in AChE activity and nitrite level in the cortex and hippocampusMishra and Goel, 2016
Ondansetron (0.1, 0.5, and 1 mg/kg per day, i.p.)Increasing current electroshock seizure in miceSingle dose and chronic administration raise the seizure threshold, chronic treatment enhances cognitive performanceChange in the influx of cations, leading to the inhibition of neuronal depolarizationJain et al., 2012
Ondansetron (0.25–4 mg/kg, i.p.)Maximal electroshock-induced seizure in ratsDecreases the duration of tonic seizures at low doses, attenuates phenytoin-induced cognitive dysfunctionFacilitation of cholinergic transmission in brainBalakrishnan et al., 2000
Zacopride (1 mg/kg, i.p.)Audiogenic seizure in DBA/2 miceIncreases seizure latency and decreases seizure severityAlteration of brain 5-HT content, densities of 5-HT binding sites, and/or sensitivity to 5-HT receptor agonistsSemenova and Ticku, 1992
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