Anticonvulsant effects reported with 5-HT3R ligands
| Category | Compound, Dose, Route of Administration | Study Design | Effects | Proposed Mechanisms | Reference |
|---|---|---|---|---|---|
| 5-HT3R agonists | m-CPBG (5 and 10 mg/kg, i.p.) | PTZ-induced seizure in mice | Potentiates the anticonvulsant effect of low doses of citalopram | 5-HT3R activation increases firing of interneurons and subsequent GABA release | Payandemehr et al., 2012 |
| m-CPBG (1 mg/kg, i.p.) | PTZ-induced seizure in mice | Potentiates the anticonvulsant effect of genistein | 5-HT3R is involved in the anticonvulsant effect of genistein | Amiri Gheshlaghi et al., 2017 | |
| SR 57227 (20–40 mg/kg, i.p.) | PTZ-induced seizure in mice | Anticonvulsant; prolongs seizure latency, reduces seizure score and mortality | 5-HT3R activation may result in GABA release in the hippocampus | Li et al., 2014 | |
| SR57227 (10 mg/kg, i.p.) | PTZ-induced seizure threshold in mice | Increases seizure threshold | 5-HT3 activation may result in GABA release | Gholipour et al., 2010 | |
| 5-HT3R antagonists | HBK-15 (20, 30, and 40 mg/kg, i.p.)a | Maximal electroshock-induced seizure in mice | Increases the threshold for tonic seizures | Combined antagonistic action at 5-HT1A/5-HT3/5-HT7 receptors and voltage-dependent sodium channels | Pytka et al., 2017 |
| Ondansetron (0.1, 0.5, and 1 mg/kg per day for 20 days, i.p.) | PTZ-induced kindling in mice | Reduction in seizure severity and associated memory deficit in a dose-dependent manner | Reduction in AChE activity and nitrite level in the cortex and hippocampus | Mishra and Goel, 2016 | |
| Ondansetron (0.1, 0.5, and 1 mg/kg per day, i.p.) | Increasing current electroshock seizure in mice | Single dose and chronic administration raise the seizure threshold, chronic treatment enhances cognitive performance | Change in the influx of cations, leading to the inhibition of neuronal depolarization | Jain et al., 2012 | |
| Ondansetron (0.25–4 mg/kg, i.p.) | Maximal electroshock-induced seizure in rats | Decreases the duration of tonic seizures at low doses, attenuates phenytoin-induced cognitive dysfunction | Facilitation of cholinergic transmission in brain | Balakrishnan et al., 2000 | |
| Zacopride (1 mg/kg, i.p.) | Audiogenic seizure in DBA/2 mice | Increases seizure latency and decreases seizure severity | Alteration of brain 5-HT content, densities of 5-HT binding sites, and/or sensitivity to 5-HT receptor agonists | Semenova and Ticku, 1992 |
↵a 1-[(2-chloro-6-methylphenoxy)ethoxyethyl]-4-(2-methoxyphenyl)piperazine hydrochloride.