Proconvulsant effects reported with 5-HT3R ligands

CategoryCompound, Dose, Route of AdministrationStudy DesignEffectsProposed MechanismReference
5-HT3R agonistBemesetron (MDL-72222) (0, 5.6, 10, and 17.0 mg/kg, i.p.)Ethanol withdrawal-induced seizure in micePotentiates severity of seizuresInhibits GABA-activated chloride channelsGrant et al., 1994
m-CPBG (40 µg, i.c.v.)Kindling model of epilepsy in ratsProlongs the duration of fully kindled seizures, facilitates the development of seizure5-HT3Rs activation mediates a fast excitatory postsynaptic potential in the amygdalaWada et al., 1997
5-HT3R antagonistGranisetron (10 mg/kg, i.p.)PTZ-induced seizure in miceDecreases seizure thresholdBlockade of 5-HT3R–mediated cation conductance in GABAergic interneurons disinhibits excitatory postsynaptic neuronsGholipour et al., 2010
Ondansetron (0.13 mg/kg, i.v.)Case report in a childDevelops generalized tonic-clonic seizures, reduces blood glucose level to 10 mg/dlPatel et al., 2011
Ondansetron (2 mg/kg, i.p.)PTZ-induced kindling model of epilepsy in micePartially reverses the anticonvulsant action and neuroprotective effect of fluvoxamineAnticonvulsant effect of fluvoxamine, at least in part, depends on enhancement of hippocampal serotoninergic transmission at 5-HT3RsAlhaj et al., 2015
Tropisetron (1 mg/kg, i.p.)PTZ-induced seizure in miceInhibits the anticonvulsant effect of citalopramBlockade of the 5-HT3R as a calcium-conducting ion channel results in inhibition of early depolarization of inhibitory interneuronsPayandemehr et al., 2012
Tropisetron (10 mg/kg, i.p.)PTZ-induced seizure in miceOffsets the anticonvulsant effect of genisteinEstrogen and 5-HT3Rs are involved in the anticonvulsant effect of genisteinAmiri Gheshlaghi et al., 2017
Tropisetron (0.25 and 2 mg/kg, i.p.)PTZ-induced seizure in miceInhibits the anticonvulsant properties of citalopramAnticonvulsive effect of citalopram is mediated at least in part through 5-HT3RsBahremand et al., 2011
  • Dashes indicate not identified or not applicable.