Proconvulsant effects reported with 5-HT3R ligands
| Category | Compound, Dose, Route of Administration | Study Design | Effects | Proposed Mechanism | Reference |
|---|---|---|---|---|---|
| 5-HT3R agonist | Bemesetron (MDL-72222) (0, 5.6, 10, and 17.0 mg/kg, i.p.) | Ethanol withdrawal-induced seizure in mice | Potentiates severity of seizures | Inhibits GABA-activated chloride channels | Grant et al., 1994 |
| m-CPBG (40 µg, i.c.v.) | Kindling model of epilepsy in rats | Prolongs the duration of fully kindled seizures, facilitates the development of seizure | 5-HT3Rs activation mediates a fast excitatory postsynaptic potential in the amygdala | Wada et al., 1997 | |
| 5-HT3R antagonist | Granisetron (10 mg/kg, i.p.) | PTZ-induced seizure in mice | Decreases seizure threshold | Blockade of 5-HT3R–mediated cation conductance in GABAergic interneurons disinhibits excitatory postsynaptic neurons | Gholipour et al., 2010 |
| Ondansetron (0.13 mg/kg, i.v.) | Case report in a child | Develops generalized tonic-clonic seizures, reduces blood glucose level to 10 mg/dl | — | Patel et al., 2011 | |
| Ondansetron (2 mg/kg, i.p.) | PTZ-induced kindling model of epilepsy in mice | Partially reverses the anticonvulsant action and neuroprotective effect of fluvoxamine | Anticonvulsant effect of fluvoxamine, at least in part, depends on enhancement of hippocampal serotoninergic transmission at 5-HT3Rs | Alhaj et al., 2015 | |
| Tropisetron (1 mg/kg, i.p.) | PTZ-induced seizure in mice | Inhibits the anticonvulsant effect of citalopram | Blockade of the 5-HT3R as a calcium-conducting ion channel results in inhibition of early depolarization of inhibitory interneurons | Payandemehr et al., 2012 | |
| Tropisetron (10 mg/kg, i.p.) | PTZ-induced seizure in mice | Offsets the anticonvulsant effect of genistein | Estrogen and 5-HT3Rs are involved in the anticonvulsant effect of genistein | Amiri Gheshlaghi et al., 2017 | |
| Tropisetron (0.25 and 2 mg/kg, i.p.) | PTZ-induced seizure in mice | Inhibits the anticonvulsant properties of citalopram | Anticonvulsive effect of citalopram is mediated at least in part through 5-HT3Rs | Bahremand et al., 2011 |
Dashes indicate not identified or not applicable.