Table 3.

Sig1R-dependent anti-seizure activity of allosteric Sig1R modulators.

Compound	Dose, mg/kg	Seizure model	Effects	References
SKF83959	2	Maximal electroshock seizure threshold test	No significant effect	Guo et al., 2015
	10		Increased the seizure threshold
	20
	40
	2	PTZ (80 mg/kg, s.c.)	No significant effect
	10		No significant effect
	20		Prolonged the latencies of clonic and generalized clonic-tonic seizures, survival time, and significantly lowered seizure scores
	40
	2	Kainic acid (30 mg/kg, i.p.)	No significant effect
	10		No significant effect
	20		No significant effect
	40		Significantly reduced seizure incidence, prolonged the latency to seizures, and shortened the duration of seizures
SOMCL-668	40	Maximal electroshock seizure threshold test	Increased the seizure threshold	Guo et al., 2015
	40	PTZ (80 mg/kg, s.c.)	Prolonged the latency time to the generalized clonic-tonic seizures and survival time
	40	Kainic acid (30 mg/kg, i.p.)	Prolonged the latency time and shortened the duration of seizures
E1R	10	PTZ (i.v. infusion)	Increased the threshold for clonic and tonic seizures	Vavers et al., 2017
	50
	10	BIC (i.v. infusion)	No significant effect
	50		Increased the threshold for clonic and tonic seizures
	75	NE-100 (75 mg/kg, i.p.)*	Significantly reduced generalized seizure count and average behavioral score
Fenfluramine (ZX008)	Maximum Tolerable Concentration	Homozygous scn1a mutant zebrafish larvae	Decreased epileptiform activity	Sourbron et al., 2017
	3 nmol	NMDA (i.c.v. administration)	Reduced rearing, hypermotility-circling, clonic convulsions, tonic seizures, and death	Rodríguez-Muñoz et al., 2018
	500 μM	Low Mg2+	Blockade of early and late epileptiform activity	Gentsch et al., 2000

^*NE-100 induced seizures in 100% of animals at a dose of 75 mg/kg (Vavers et al., 2017). Phenytoin, ropizine, SCH23390, and SKF38393 are not included in the table because the seizure modulating activities of these compounds are not shown to be significantly blocked by the selective Sig1R ligands.