Table 1.
Prostanoid and cannabinoid receptors in seizure disorders.
| Receptor | G protein | Recent studies and therapeutic outcomes | References |
|---|---|---|---|
| EP1 | Gq/11 | EP1 antagonist SC-19220 (10 nmol, i.c.v.) 15 min before PTZ injection (60 mg/kg, i.p.) reduced PTZ-provoked acute seizures in adult male Wistar rats. | Oliveira et al., 2008 |
| Treatment with EP1 antagonist SC-51089 (10 mg/kg, i.p., b.i.d.) starting 30 min before the first pilocarpine injection interrupted seizure-promoted expression of efflux transporter P-glycoprotein at the blood-brain barrier following lithium-pilocarpine-induced status epilepticus in adult female Wistar rats and restored the anticonvulsant effect of a low dose of phenobarbital (6 mg/kg, i.p.). | Pekcec et al., 2009 | ||
| Pre-Treatment with EP1 antagonist SC-51089 (3-30 mg/kg, i.p.) significantly decreased the seizure severity in adult male NMRI mice after amygdala kindling. | Fischborn et al., 2010 | ||
| Genetic ablation of EP1 receptor increased seizure threshold and showed anti-inflammatory and neuroprotective effects after systemic administration of kainate in male adult C57BL/6 mice. | Rojas et al., 2014 | ||
| Pre-treatment with EP1 antagonist ONO-8713 (10 mg/kg, s.c.) 30 min before PTZ injection (60 mg/kg, i.p.) attenuated, whereas EP1 agonist ONO-DI-004 (10 mg/kg, s.c.) exacerbated PTZ-induced seizures in adult male Swiss mice. | Reschke et al., 2018 | ||
| EP2 | Gs | Treatment with EP2 selective antagonist TG4-155 (5 mg/kg, i.p.) reduced neuronal injury in the hippocampus after pilocarpine (280 mg/kg, i.p.)-induced status epilepticus in male adult C57BL/6 mice. | Jiang et al., 2012 |
| Post-treatment with EP2 antagonist TG6-10-1 (5 mg/kg, i.p.) brought extensive benefits following status epileptics in pilocarpine (280 mg/kg, i.p.)-treated male adult C57BL/6 mice, i.e., reduction in delayed mortality, acceleration of recovery from weight loss and functional impairment, prevention of the blood-brain barrier breakdown, and decrease in neuronal inflammation and injury in the hippocampus. | Jiang et al., 2013; Jiang et al., 2015 | ||
| Post-treatment with TG6-10-1 treatment (5 mg/kg, i.p.) was neuroprotective and accelerated functional recovery after status epilepticus in male adult Sprague Dawley rats treated by DFP (9.5 mg/kg, i.p.). | Rojas et al., 2015 | ||
| Post-treatment with TG6-10-1 (5 mg/kg, i.p.) prevented status epilepticus-induced deficits in the novel object recognition task in male adult Sprague Dawley rats. | Rojas et al., 2016 | ||
| Post-treatment with TG6-10-1 (5 mg/kg, i.p., b.i.d.) reduced prolonged seizure-promoted functional deficits, cytokine induction, reactive gliosis, blood-brain barrier disruption, and hippocampal damage in adult male C57BL/6 mice treated by kainate (30 mg/kg, i.p.). | Jiang et al., 2019 | ||
| EP3 | Gi/o | EP3 antagonist L-826266 (1 nmol, i.c.v.) 15 min before PTZ injection (60 mg/kg, i.p.) increased the latency for clonic seizures induced by PTZ in adult male Wistar rats. | Oliveira et al., 2008 |
| Pre-treatment with EP3 antagonist ONO-AE3-240 (10 mg/kg, s.c.) 30 min before PTZ injection (60 mg/kg, i.p.) attenuated, whereas EP3 agonist ONO-AE-248 (10 mg/kg, s.c.) potentiated PTZ-induced seizures in adult male Swiss mice. | Reschke et al., 2018 | ||
| EP4 | Gs | EP4 antagonist L-161982 (750 pmol, i.c.v.) 15 min before PTZ injection (60 mg/kg, i.p.) increased the latency for PTZ-evoked acute seizures in adult male Wistar rats. | Oliveira et al., 2008 |
| FP | Gq/11 | Intracisternal administration of PGF2α (700 ng/35 g) after pre-treatment with COX inhibitor indomethacin (10 mg/kg, i.p.) prevented seizures and decreased neuronal injury in the hippocampus after systemic injection of kainate for seizure induction in adult male ICR mice; PGF2α alone had no effect on kainate-induced seizures in these animals. | Kim et al., 2008 |
| Intracisternal injection of FP antagonist AL-8810 (10 or 50 ng/35 g) 20 min before kainate injection aggravated seizure activity in adult male ICR mice in a dose-dependent manner. | Kim et al., 2008 | ||
| Intracisternal administration of PGF2α (700 ng) 20 min before kainate injection reduced seizure activity and mortality in immature CD-1 mice. | Chung et al., 2013 | ||
| DP1 | Gs | PGD2 (5 μg, i.c.v.) or an active analog ZK-118.182 (1-100 ng, i.c.v.) 5 min before PTZ injection (60 mg/kg, i.p.) delayed the onset of generalized convulsions and reduced mortality in adult male Wistar rats. | Akarsu et al., 1998 |
| Supression of PGD2 activity by AH-6809 (50 ng, i.c.v.) 20 min before PTZ injection (60 mg/kg, i.p.) or inhibition of PGD2 synthesis by sodium selenite (0.2 μg, i.c.v.) 15 min before PTZ injection (60 mg/kg, i.p.) increased the seizure incidence and intensity in adult male Wistar rats. | Akarsu et al., 1998 | ||
| Genetic ablation of DP1 receptor delayed seizure onset, reduced the duration of generalized tonic-clonic seizures, and decreased number of seizure spikes in adult male C57BL/6 mice treated by PTZ. | Kaushik et al., 2014 | ||
| TP | Gq/11 | TP activation by U-46619 (300 μg/kg, s.c.) 30 min before the injection of PTZ (60 mg/kg; i.p.) increased the latency for PTZ-induced myoclonic jerks and tonic-clonic seizures in adult female C57BL/6 mice. | Freitas et al., 2018 |
| TP antagonist, SQ-29548 (up to 300 μg/kg, i.p.) 30 min before the injection of PTZ (60 mg/kg; i.p.) neither modified PTZ-induced seizures nor blunted the anticonvulsant effect of the agonist U-46619 in adult female C57BL/6 mice. | Freitas et al., 2018 | ||
| CB1 | Gi/o | Adult male C57BL/6 mice lacking CB1 showed decreased seizure threshold in kainate model of temporal lobe epilepsy. | Marsicano et al., 2003 |
| Non-selective CB agonist WIN 55212-2 showed dose-dependent anticonvulsant effects in hippocampal neuronal culture models of status epilepticus and acquired epilepsy; whereas the anticonvulsant action of WIN 55212-2 in these models was specifically blocked by a CB1 antagonist SR141716. | Blair et al., 2006 | ||
| Genetic ablation of CB1 receptor or pre-treatment with the antagonist SR141716 (10 mg/kg) increased seizure severity without altering seizure-promoted cell proliferation and neuronal death after pilocarpine injection in male adult C57BL/6 mice. | Kow et al., 2014 | ||
| Pre-treatment with CB1 agonist CP55940 (0.3 mg/kg, i.p.) did not show any obvious effect on pilocarpine-induced seizures in male adult C57BL/6 mice. | Kow et al., 2014 | ||
| Treatment with CB1 selective inverse agonist AM251 (20 mg/kg, i.p.) 60 min before kainate injection (30 mg/kg, i.p.) shortened the latency to onset of generalized tonic-clonic seizures and increased mortality in adult male and female C57BL/6 mice. | Sugaya et al., 2016 | ||
| CB2 | Gi/o | CB2 inverse agonist AM630 (2 mg/kg, i.p.), when co-administered with non-selective CB receptor agonist WIN 55212-2 (21 mg/kg, i.p.), but not by itself alone, showed considerable antiepileptic effects in the maximal dentate activation model of partial epilepsy in adult male Wistar rats. | Rizzo et al., 2014 |
| Co-treatment with CB2 selective inverse agonist AM630 (2 mg/kg, i.p.) exacerbated the susceptibility of AM251(20 mg/kg, i.p.)-treated adult male and female C57BL/6 mice to kainate (30 mg/kg, i.p.)-induced seizures. | Sugaya et al., 2016 | ||
| Deletion of both CB1 and CB2, but not either CB1 or CB2 alone, showed spontaneous seizures or handling-induced seizures in adult male and female C57BL/6 mice. | Rowley et al., 2017 |
Abbreviations: DFP, diisopropyl fluorophosphate; PTZ, pentylenetetrazol.