TABLE 2.
Perceived molecular targets of clinically used antiseizure medications. Adapted from Rogawski and Löscher (2004), Rogawski et al. (2016), Sills and Rogawski (2020), and Löscher and Klein (2021a).
| Mechanistic classes of antiseizure medications | Antiseizure medications that belong to this mechanistic class | |
|---|---|---|
| Modulators of voltage-gated sodium channels | ||
| Increase of fast inactivation (transient sodium current; INaT) | Phenytoin, fosphenytoin, a carbamazepine, oxcarbazepine, b eslicarbazepine acetate, c lamotrigine; possibly topiramate, zonisamide, rufinamide, brivaracetam | |
| Increase of slow inactivation | Lacosamide | |
| Block of persistent sodium currents (INaP) | Cenobamate, lacosamide, carbamazepine, oxcarbazepine, eslicarbazepine, lamotrigine, phenytoin, topiramate, valproate, gabapentin, cannabidiol | |
| Blockers of voltage-gated calcium channels (T-type) | ||
| High-voltage activated (HVA) | Phenobarbital, phenytoin, levetiracetam | |
| Low-voltage activated T-type (Cav3) | Ethosuximide (Cav3.2 > Cav3.1), methsuximide, eslicarbazepine (Cav3.2), possibly valproate | |
| Activators of voltage-gated potassium channels (K v 7) | Retigabine (ezogabine) | |
| Modulators of GABA-mediated inhibition | ||
| Allosteric modulators of GABAA receptors | Phenobarbital, primidone, stiripentol, benzodiazepines, (including clonazepam, clobazam, diazepam, lorazepam, and midazolam), topiramate, felbamate, retigabine (ezogabine), cenobamate | |
| Inhibitors of GAT1 GABA transporter | Tiagabine | |
| Inhibitors of GABA transaminase (GABA-T) | Vigabatrin | |
| Activators of Glutamic acid decarboxylase (GAD) | Possibly valproate, gabapentin, pregabalin | |
| Inhibitors of ionotropic glutamate receptors | ||
| Antagonists of NMDA receptors | Felbamate, topiramate, possibly valproate | |
| Antagonists of AMPA receptors | Perampanel, phenobarbital, levetiracetam, topiramate | |
| Modulators of the presynaptic release machinery | ||
| SV2A | Levetiracetam, brivaracetam | |
| α2δ subunit of calcium channels | Gabapentin, pregabalin | |
| Inhibitors of carbonic anhydratase | Acetazolamide, sulthiame, topiramate, zonisamide, possibly lacosamide | |
| Serotonin-releasing agents | Fenfluramine | |
| Disease-specific modulators | ||
| Inhibitors of mTORC1 signaling d | Everolimus | |
| Lysosomal enzyme replacement e | Cerliponase alfa (recombinant tripeptidyl peptidase 1) | |
| Mixed/unknown | Valproate, felbamate, topiramate, zonisamide, rufinamide, adrenocorticotrophin (ACTH), cannabidiol, cenobamate, potassium bromide | |
a
Fosphenytoin is a prodrug for phenytoin.
b
Oxcarbazepine serves largely as a prodrug for licarbazepine, mainly S-licarbazepine (eslicarbazepine).
c
Eslicarbarbazepine acetate is a prodrug for S-licarbazepine (eslicarbazepine).
d
In patients with epilepsy due to tuberous sclerosis complex (TSC).
e
In patients with epilepsy due to neuronal ceroid lipofuscinosis type 2 (CLN2).