Molecular targets of clinically used ASDs
Adapted from Rogawski and Löscher (2004), Rogawski et al. (2016), and Sills and Rogawski (2020)
| Molecular target | ASDs that act on target |
|---|---|
| Voltage-gated ion channels | |
| Voltage-gated sodium channels | Phenytoin, fosphenytoin,a carbamazepine, oxcarbazepine,b eslicarbazepine acetate,c lamotrigine, lacosamide; possibly topiramate, zonisamide, rufinamide |
| Voltage-gated calcium channels (T-type) | Ethosuximide |
| Voltage-gated potassium channels (Kv7) | Retigabine (ezogabine) |
| GABA-mediated inhibition | |
| GABAA receptors | Phenobarbital, primidone, stiripentol, benzodiazepines, (including diazepam, lorazepam, midazolam and clonazepam), possibly topiramate, felbamate, retigabine (ezogabine) |
| GAT1 GABA transporter | Tiagabine |
| GABA transaminase | Vigabatrin |
| Glutamic acid decarboxylase | Possibly valproate, gabapentin, pregabalin |
| Presynaptic release machinery | |
| SV2A | Levetiracetam, brivaracetam |
| α2δ subunit of calcium channels | Gabapentin, pregabalin |
| Ionotropic glutamate receptors | |
| AMPA receptor | Perampanel |
| Carbonic anhydratase inhibition | Acetazolamide, topiramate, zonisamide, possibly lacosamide |
| Disease-specific | |
| mTORC1 signalingd | Everolimus |
| Lysosomal enzyme replacemente | Cerliponase alfa (recombinant tripeptidyl peptidase 1) |
| Mixed/unknown | Valproate, felbamate, topiramate, zonisamide, rufinamide, adrenocorticotrophin (ACTH), cannabidiol, cenobamate |
AMPA, α-amino-3-hydroxy-5-methyl-4-isoxazole-propionate.
↵a Fosphenytoin is a prodrug for phenytoin.
↵b Oxcarbazepine serves largely as a prodrug for licarbazepine, mainly S-licarbazepine.
↵c Eslicarbarbazepine acetate is a prodrug for S-licarbazepine.
↵d In patients with epilepsy because of tuberous sclerosis complex (TSC).
↵e In patients with epilepsy because of neuronal ceroid lipofuscinosis type 2.