. 2021 Oct 27;12:730257. doi: 10.3389/fphar.2021.730257

TABLE 1.

Antiseizure potencies of multi-target antiseizure medications (ASMs) in mouse and rat models. Some ASMs that are thought to act predominantly at one target are shown for comparison. Data are from Gladding et al. (1985); Löscher (1980), Löscher et al. (1986); Löscher and Nolting (1991), Löscher and Hönack (1993); Dalby and Nielsen (1997); Otsuki et al. (1998), Barton et al. (2001), Riban et al. (2002); Stöhr et al. (2007); Hanada et al. (2011), Bankstahl et al. (2013), Twele et al. (2015); Duveau et al. (2016); Klitgaard et al. (2016); Wu et al. (2019), Leclercq et al. (2020), Löscher et al. (2021), and the PANAChE database of the NINDS. Abbreviations: i.h., intrahippocampal; MES, maximal electroshock seizure; NE, not effective at tolerated doses; p.o., orally; PTZ, pentylenetetrazole; SRS, spontaneous recurrent seizures; SV, synaptic vesicle protein.

Compound	Targets	ED50 (mg/kg i.p.) at time of peak effect
		MES		s.c. PTZ		6-Hz (mice) ^a			SRS in i.h kainate model (mice)	Amygdala or hippocampal kindled seizures (rats) ^b
		MES		s.c. PTZ
		Mice	Rats	Mice	Rats	22 mA	32 mA	44 mA
Multi-target ASMs
Padsevonil ^c	SV2A,B,C and GABA_A receptors	92.8		4.8				0.16	∼0.5	2.43
Cenobamate	GABA_A receptors and persistent Na⁺ currents	9.8	2.9	28.5		11	17.9	16.5		16.4
Felbamate	GABA_A and NMDA receptors, transient Na⁺ currents, voltage-gated Ca²⁺ channels	35.5	35	126	>250 (p.o.)	13.1	69.5	241		296
Retigabine (ezogabine)	Voltage-gated K⁺ (KCNQ) channels, GABA_A receptors	9.3	5.1	13.5			26	33		3.2
Valproate	GABA synthesis, NMDA receptors, persistent Na⁺ currents, low-voltage activated T-type Ca²⁺ channels	271	140	149	195	41.5	126	310	∼330	190
Topiramate	GABA_A and NMDA receptors, transient and persistent Na⁺ currents	33	11.5	NE			NE			13.3
Phenobarbital	GABA_A and AMPA receptors, voltage-gated Ca²⁺ channels	21.8	12	13.2	41		14.8	18.3	25	16
Single-target ASMs
Phenytoin	Voltage-activated Na⁺ channels	9.5	13	NE	NE	9.4	NE	NE	NE	30
Carbamazepine	Voltage-activated Na⁺ channels	8.8	6	NE	NE		47.9		NE	8
Lamotrigine	Voltage-activated Na⁺ channels	7.5	4,4	NE		4.4	NE	NE	NE	∼3.4
Lacosamide	Voltage-activated Na⁺ channels	4.5	3.9 (p.o.)	NE	NE		9.9			13.5
Brivaracetam	SV2A	113		30				4.4		∼80
Levetiracetam ^d	SV2A	NE		NE		4.6	19.4	1,089	420	∼54
Ethosuximide	Low-voltage activated T-type Ca²⁺ channels	NE	NE	130	140	87	167	NE		NE
Vigabatrin ^e	GABA metabolism	NE		940			>250		50	600
Perampanel (p.o.)	AMPA receptors	1.6		0.94			2.1	2.8	0.7	∼10

Potency varies with mouse strain used.

For generalized convulsive seizures (ED₅₀s are higher for focal seizures).

Not approved for treatment of epilepsy.

Note that levetiracetam also acts via other targets (see text).

Much more potent after chronic administration.