19 Pharmacopeia

Gail D. Anderson

Department of Pharmacy, UW Regional Epilepsy Center, University of Washington, Seattle, WA, USA

Table 19.1. Approved indications of the antiepileptic drugs.

Table 19.2. Chemistry and pharmacology of the antiepileptic drugs.

Drug	Chemical structure	Proposed mechanism of action
Acetazolamide	5-Acetamido-1,3,4-thiadiazole-2-sulfonamide	Inhibits carbonic anhydrase
Carbamazepine	5-Carbamoil-5H-dibenz[b,f ]azepine	Inhibits voltage-gated sodium channels Stabilizes neuronal membranes and limits sustained repetitive firing
Clobazam	7-chloro-1-methyl-5-phenyl-1H-1,5-benzodiazepine-2,4(3H,5H)dione	Enhances GABA_A receptor-mediated chloride currents
Clonazepam	5-(2-Chlorophenyl)-1,3-dihydro-7-nitro-2H-1,4 benzodiazepin-2-one	Enhances GABA_A receptor-mediated chloride currents
Diazepam	7-Chloro-1,3-dihydro-1-methyl-5-phenyl-1,4 benzodiazepin-2(3H)-one	Enhances GABA_A receptor-mediated chloride currents
Eslicarbazepine acetate	S-(−)-10-acetoxy-10,11-dihydro-5H-dibenzo[b,f]azepine-5-carboxamide	Voltage-gated sodium channel blocker
Ethosuximide	2-Ethyl-2-methylsuccinimide	Attenuates voltage-sensitive calcium channels
Ezogabine	N-(2-amino-4-(4-fluorobenzyl-amino)-phenyl) carbamic acid ethyl ester	Opens/activates voltage-gated potassium channels (KCNQ2/3, KCNQ3/6) Potentiates GABA-evoked currents
Felbamate	2-Phenyl-1,3-propanediol dicarbamate	Inhibits voltage-gated sodium channels Inhibits calcium currents through NMDA receptors Enhances GABA_A receptor-mediated chloride channels
Gabapentin	1-Aminomethyl-cyclohexane acetic acid	Binds to α₂δ subunit of the L-type calcium channel Increases GABA levels by increasing GABA turnover Inhibits monoamine neurotransmitter release Decreases sustained repetitive firing
Lacosamide	(R)-2-acetamido-N-benzyl-3-methoxypropionamide	Enhances slow inactivation of sodium channels
Lamotrigine	3,5-Diamino-6-(2,3-dichlorophenyl)-1,2,4-triazine	Inhibits sodium currents Inhibits high-threshold activated calcium channels
Levetiracetam	(S)-α-ethyl-2-oxo-1-pyrrolidine acetamide	Limits calcium influx through an N-type voltage-sensitive calcium channel Binds to synaptic vesicle protein 2A
Lorazepam	7-Chloro-5(2-chlorophenyl)-1,3-dihydro-3-dihydroxy-2H-1,4-benzoidazepin-2-one	Enhances GABA_A receptor-mediated chloride currents
Oxcarbazepine	10,11-Dihydro-10-oxo-carbamazepine	Active metabolite, 10-OH-carbazepine, inhibits sustained repetitive firing
Perampanel		Reduces neuronal excitation via the noncompetitive antagonism of the ionotropic AMPA-glutamate receptor on postsynaptic neurons
Phenobarbital	5-Ethyl-5-phenylbarbituric acid	Enhances GABA_A receptor-mediated chloride currents
Phenytoin	5,5-Diphenylhydantoin	Inhibits voltage-gated sodium channels Stabilizes neuronal membranes and limits sustained repetitive firing
Pregabalin	S-(+)-3-aminomethylhexanoic acid; Isobutyl-γ-aminobutyric acid	Selective inhibitor of L-type voltage-gated calcium channels containing the α₂δ subunit
Primidone	5-Ethyldihydro-5-phenyl-4,6 (1H,5H) pyrimidine-dione	Enhances GABA_A receptor-mediated chloride currents
Rufinamide	1-(2,6-Difluorophenyl)methyl-1H-1,2,3-triazole-4-carboxamide	Sodium channel blocker
Stiripentol	4,4-Dimethyl-1-[(3,4 methylenedioxy) phenyl]-1-penten-3-ol	Enhances GABAergic neurotransmission by increasing the release of GABA and the duration of the activation of GABA_A receptors
Tiagabine	(−)-R-1-[4,4-bis(3-methyl-2-thienyl)-3-butenyl]-3-piperidinecarboxylic acid	Selective blocker of neuronal and glial GABA transporters resulting in increased brain GABA levels
Topiramate	2,3:4,5-bis-O-(1-methylethylidene)-β–D-fructopyranose sulfamate	Blocks sustained repetitive firing and inhibits sodium currents Decreases glutamate-mediated excitation via the AMPA/kainate receptor Enhances GABA_A currents Potentiates hyperpolarizing potassium currents Inhibits high-threshold activated calcium channels Inhibits carbonic anhydrase
Valproate	2-Propylpentanoic acid	Attenuates voltage-sensitive calcium channels, inhibits sodium channels, and stabilizes neuronal membranes Enhances GABAergic-mediated inhibition
Vigabatrin	4-Amino-5-hexenoic acid; γ-vinyl GABA	Irreversibly inhibits GABA transaminase, resulting in increased brain GABA levels
Zonisamide	1,2-Benzisoxazole-3-methane sulfonamide	Blocks sustained repetitive firing through an effect on voltage-sensitive sodium channels Reduces T-type calcium currents Alters ligand binding to GABA_A receptor Inhibits carbonic anhydrase