Drug Reference for FDA Approved Epilepsy Drugs @ Neurotransmitter.net


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Generic Name:
acetazolamide

Trade Name:
Diamox ® [Wyeth]

IUPAC Name:
N-(5-sulfamoyl-1,3,4-
thiadiazol-
2-yl)ethanamide

Dosage Forms/Routes:
Tablet/oral;
Injectable/injection;
Capsule (extended release)/oral

Database Search Links:
[PubMed]

[Search PubMed for
Randomized Controlled Trials
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[
PubChem]
[PDSP Ki database]

Initial Approval:
07/27/1953


Manufacturers:

[FDA Search]

Product Insert:
[Link]

RxList:
[Link]

Epocrates:
[Link]

Empirical Formula:
C4H6N4O3S2

Molecular Mass:
222.248 g/mol

Indications:
For adjunctive treatment of: edema due to congestive heart failure; drug-induced edema; centrencephalic epilepsies (petit mal, unlocalized seizures); chronic simple (open-angle) glaucoma, secondary glaucoma, and preoperatively in acute angle-closure glaucoma where delay of surgery is desired in order to lower intraocular pressure. Acetazolamide is also indicated for the prevention or amelioration of symptoms associated with acute mountain sickness in climbers attempting rapid ascent and in those who are very susceptible to acute mountain sickness despite gradual ascent.

Possible Mechanisms of Action:
Acetazolamide inhibits carbonic anhydrase isozymes CA II (1), CA III (2), CA IV (3), CA VA (4), CA VB (5), CA VI (6), CA VII (7), CA IX (1), CA XII (8), CA XIII (9), and CA XIV (10).

Chemical Class:
arylsulfonamide analog

PubChem 2D Structure:

Generic Name:
carbamazepine

Trade Name:
Tegretol ® [Novartis]

Common Chemical Name:
5H-dibenz(b,f)azepine-5-
carboxamide

Major Metabolite:
carbamazepine-10,11-epoxide

Dosage Forms/Routes:
Tablet/oral;
Tablet/chewable oral;
Suspension/oral;

Capsule (extended release)/oral

Database Search Links:
[PubMed]

[Search PubMed for
Randomized Controlled Trials
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[
PubChem]
[PDSP Ki database]

Initial Approval:
03/11/1968


Manufacturers:

[FDA Search]

Product Insert:
[Link]

RxList:
[Link]

Epocrates:
[Link]

Empirical Formula:
C15H12N2O

Molecular Mass:
236.269 g/mol

Indications:
Epilepsy:
Carbamazepine is indicated for use as an anticonvulsant drug. Evidence supporting efficacy of carbamazepine as an anticonvulsant was derived from active drug-controlled studies that enrolled patients with the following seizure types:

Partial seizures with complex symptomatology (psychomotor, temporal lobe). Patients with these seizures appear to show greater improvement than those with other types.

Generalized tonic-clonic seizures (grand mal).

Mixed seizure patterns which include the above, or other partial or generalized seizures. Absence seizures (petit mal) do not appear to be controlled by carbamazepine.

Trigeminal Neuralgia: Carbamazepine is indicated in the treatment of the pain associated with true trigeminal neuralgia.

Beneficial results have also been reported in glossopharyngeal neuralgia.

This drug is not a simple analgesic and should not be used for the relief of trivial aches or pains.

Possible Mechanisms of Action:
Carbamazepine inhibits voltage-gated sodium channels in a use- dependent manner (11). The drug is an antagonist at adenosine A1 receptors (12, 13, 14). Carbamazepine may be an agonist at adenosine A2A and/or A2B receptors (14). Carbamazepine also inhibits adenylyl cyclase via an unidentified mechanism (15). In addition, carbamazepine may be a histone deacetylase inhibitor (63).

Chemical Class:
tricyclic iminostilbene derivative

PubChem 2D Structure:

"3D" Structure (Requires Chime):
[
Link] 

Generic Name:
clonazepam

Trade Name:
Klonopin ® [
Roche]

IUPAC Name:
6-(2-chlorophenyl)-9-nitro-
2,5-diazabicyclo[5.4.0]undeca-
5,8,10,12-tetraen-3-one

Major Metabolite:
7-aminoclonazepam

Dosage Forms/Routes:
Tablet/oral;
Orally disintegrating tablet/oral

Database Search Links:
[PubMed]

[Search PubMed for
Randomized Controlled Trials
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[
PubChem]
[PDSP Ki database]

Initial Approval:
06/04/1975


Manufacturers:

[FDA Search]

Product Insert:
[Link]

RxList:
[Link]

Epocrates:
[Link]

Empirical Formula: C15H10ClN3O3

Molecular Mass:
315.711 g/mol

Indications:
Alone or as an adjunct in the treatment of the Lennox-Gastaut syndrome (petit mal variant), akinetic seizures, and myoclonic seizures; in patients with absence seizures (petit mal) who have failed to respond to succinimides, clonazepam may be useful; panic disorder

Possible Mechanism of Action:
Clonazepam is a nonselective benzodiazepine agonist (16).

Chemical Class:
3-hydroxy benzodiazepine

PubChem 2D Structure:

"3D" Structure (Requires Chime):
[
Link] 

Generic Name:
clorazepate dipotassium

Trade Name:
Tranxene ® [Ovation]

IUPAC Name:
dipotassium 9-chloro-3-oxo-6-
phenyl-2,5-
diazabicyclo[5.4.0]undeca-
5,8,10,12-tetraene-4-carboxylic
acid hydroxide

Major Metabolites:
nordiazepam;
oxazepam

Dosage Forms/Routes:
Tablet/oral;
Capsule/oral

Database Search Links:
[PubMed]

[Search PubMed for
Randomized Controlled Trials
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[
PubChem]
[PDSP Ki database]

Initial Approval:
06/23/1972


Manufacturers:

[FDA Search]

Product Insert:
[Link]

RxList:
[Link]

Epocrates:
[Link]

Empirical Formula:
C16H12ClK2N2O4+

Molecular Mass:
409.927 g/mol

Indications:
Adjunctive therapy in the management of partial seizures; anxiety disorders or short-term relief of the symptoms of anxiety; withdrawal symptoms of acute alcoholism

Possible Mechanism of Action:
Clorazepate is a nonselective benzodiazepine agonist (17).

Chemical Class:
2-keto benzodiazepine

PubChem 2D Structure:

"3D" Structure (Requires Chime):
[Link] 

Generic Name:
diazepam

Trade Name:
Valium ® [
Roche]

IUPAC Name:
9-chloro-2-methyl-6-phenyl-
2,5-diazabicyclo[5.4.0]undeca-
5,8,10,12-tetraen-3-one

Major Metabolites:
nordiazepam;
temazepam;
oxazepam

Dosage Forms/Routes:
Tablet/oral;
Injectable/injection;
Concentrate/oral;
Gel/rectal

Database Search Links:
[PubMed]

[Search PubMed for
Randomized Controlled Trials
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[
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[PDSP Ki database]

Initial Approval:
11/15/1963 


Manufacturers:

[FDA Search]

Product Insert:
[Valium Tablet]
[Injectable]
[Gel]
[Concentrate]

RxList:
[Link]

Epocrates:
[Link]

Empirical Formula:
C16H13ClN2O

Molecular Mass:
284.74 g/mol

Indications:
Adjunct for convulsive disorders; anxiety disorders or short-term relief of the symptoms of anxiety; symptomatic relief of acute alcohol withdrawal; adjunct for the relief of skeletal muscle spasm due to reflex spasm to local pathology, spasticity caused by upper motor neuron disorders, athetosis, and stiff-man syndrome
.

Diazepam is useful premedication for relief of anxiety and tension in patients who are to undergo surgical procedures.

Diazepam injection is a useful adjunct in status epilepticus and severe recurrent convulsive seizures.

Diazepam is indicated as an adjunct prior to endoscopic procedures if apprehension, anxiety, or acute stress reactions are present, and to diminish the patient's recall of the procedures.

Possible Mechanisms of Action:
Diazepam is a nonselective benzodiazepine agonist (18). Diazepam is also an agonist at peripheral benzodiazepine receptors (19).

Chemical Class:
2-keto benzodiazepine

PubChem 2D Structure:

"3D" Structure (Requires Chime):
[Link] 

Generic Name:
divalproex sodium

Trade Name:
Depakote ® [
Abbott Labs]

IUPAC Name:
sodium; 2-propylpentanoate;
2-propylpentanoic acid

Major Metabolites:
3-keto-valproic acid;
trans-2-ene valproic acid;
valproic acid glucuronide

Dosage Forms/Routes:
Tablet (delayed release)/oral;
Capsule (delayed release pellets)/oral;
Tablet (extended release)/oral

Database Search Links:
[PubMed]

[Search PubMed for
Randomized Controlled Trials
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[
PubChem]
[PDSP Ki database]

Initial Approval:
03/10/1983


Manufacturers:

[FDA Search]

Product Insert:
[Depakote Capsule]
[Depakote Tablet]
[Depakote ER Tablet]

RxList:
[Link]

Epocrates:
[Link]

Empirical Formula:
C16H31NaO4

Molecular Mass:
310.405 g/mol

Indications:
Depakote ER Only: Manic episodes associated with bipolar disorder; prophylaxis of migraine headaches

All dosage forms: Monotherapy and adjunctive therapy in the treatment of patients with complex partial seizures that occur either in isolation or in association with other types of seizures; sole or adjunctive therapy in the treatment of simple and complex absence seizures; adjunct for the treatment of patients with multiple seizure types that include absence seizures

Possible Mechanisms of Action:
Divalproex is a histone deacetylase inhibitor (20). The enhancement of gamma-aminobutyric acid (GABA) activity by divalproex is possibly due to the downregulation of GAT-1 and GAT-3 GABA transporter proteins by the drug (21); the cause of this effect is currently unknown. Divalproex also inhibits succinate semialdehyde dehydrogenase (22).
At voltage-gated sodium channnels, divalproex shifts the voltage dependence of steady-state inactivation to more hyperpolarized potentials (23); the degree to which this action occurs at therapeutically relevant concentrations in humans is currently not known (24). Finally, divalproex may inhibit T-type calcium channels (25).

Chemical Class:
carboxylic acid derivative

PubChem 2D Structure:

"3D" Structure (Requires Chime):
[Link] 

Generic Name:
ethosuximide

Trade Name:
Zarontin ® [Pfizer]

IUPAC Name:
3-ethyl-3-methyl-pyrrolidine-
2,5-dione

Major Metabolites:
2-(1-hydroxyethyl)-2-
methylsuccinimide;
2-ethyl-3-hydroxy-2-
methylsuccinimide

Dosage Forms/Routes:
Capsule/oral;
Syrup/oral

Database Search Links:
[PubMed]

[Search PubMed for
Randomized Controlled Trials
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[
PubChem]
[PDSP Ki database]

Initial Approval:
11/02/1960


Manufacturers:

[FDA Search]

Product Insert:
[Link 1] (Capsule)
[Link 2] (Syrup)

RxList:
[Link]

Epocrates:
[Link]

Empirical Formula:
C7H11NO2

Molecular Mass:
141.168 g/mol

Indications:
The control of absence (petit mal) epilepsy

Possible Mechanisms of Action:
Ethosuximide is a T-type calcium channel blocker (26, 30). The drug may also reduce noninactivating Na+ currents and Ca2+- activated K+ currents in thalamic and cortical neurons (31, 32).

Chemical Class:
succinimide derivative

PubChem 2D Structure:

"3D" Structure (Requires Chime):
[
Link] 

Generic Name:
felbamate

Trade Name:
Felbatol ® [MedPointe]

IUPAC Name:
(3-carbamoyloxy-2-phenyl-
propyl) aminoformate

Major Metabolite:
3-carbamoyl-2-phenylpropionic acid

Dosage Forms/Routes:
Tablet/oral;
Suspension/oral

Database Search Links:
[PubMed]

[Search PubMed for
Randomized Controlled Trials
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[
PubChem]
[PDSP Ki database]

Initial Approval:
07/29/1993


Manufacturers:

[FDA Search]

RxList:
[Link]

Epocrates:
[Link]

Empirical Formula:
C11H14N2O4

Molecular Mass:
238.24 g/mol

Indications:
Felbamate is not indicated as a first line antiepileptic treatment.

Felbamate is recommended for use only in those patients who respond inadequately to alternative treatments and whose epilepsy is so severe that a substantial risk of aplastic anemia and/or liver failure is deemed acceptable in light of the benefits conferred by its use.

If these criteria are met and the patient has been fully advised of the risk and has provided written, informed consent, felbamate can be considered for either monotherapy or adjunctive therapy in the treatment of partial seizures, with and without generalization, in adults with epilepsy and as adjunctive therapy in the treatment of partial and generalized seizures associated with Lennox-Gastaut syndrome in children.

Possible Mechanisms of Action:
Felbamate inhibits NMDA channel currents in a use- dependent manner (27). It also slows the recovery of desensitized NMDA channels (27).
Felbamate's interaction with NMDA receptor complexes is not voltage dependent (28). The drug preferentially acts at NMDA receptors that contain the NR1 and NR2B subunits (28). In addition, felbamate is a weak positive modulator of GABA-A receptor Cl- currents (43).

Chemical Class:
carbamate ester of 2-phenyl-1,3-propanediol

PubChem 2D Structure:

Generic Name:
fosphenytoin sodium

Trade Name:
Cerebyx ® [Pfizer]

IUPAC Name:
disodium 5,5-diphenyl-3-
(phosphonatooxymethyl)
imidazolidine-2,4-dione

Major Metabolites:
phenytoin

Dosage Forms/Routes:
Injectable/injection

Database Search Links:
[PubMed]

[Search PubMed for
Randomized Controlled Trials
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[
PubChem]
[PDSP Ki database]

Initial Approval:
08/05/1996


Manufacturers:

[FDA Search]

Product Insert:
[Link]

RxList:
[Link]

Epocrates:
[Link]


Empirical Formula:
C16H13N2Na2O6P

Molecular Mass:
406.238 g/mol

Indications:
Fosphenytoin is indicated for short-term parenteral administration when other means of phenytoin administration are unavailable, inappropriate or deemed less advantageous. The safety and effectiveness of fosphenytoin in this use has not been systematically evaluated for more than 5 days.

Fosphenytoin can be used for the control of generalized convulsive status epilepticus and prevention and treatment of seizures occurring during neurosurgery. It can also be substituted, short-term, for oral phenytoin.

Possible Mechanisms of Action:
Fosphenytoin is a prodrug for phenytoin. Phenytoin inhibits voltage-gated sodium channels in a use- dependent manner (11). Phenytoin is also a low affinity inhibitor at T-type calcium channels that contain the alpha1H subunit (29). In addition, phenytoin inhibits the persistent Na+ current (INaP) (47).

Chemical Class:
hydantoin


PubChem 2D Structure:

Generic Name:
gabapentin

Trade Name:
Neurontin ® [Pfizer]

IUPAC Name:
2-[1-
(aminomethyl)cyclohexyl]acetic acid

Major Metabolite:
gabapentin is excreted unchanged in urine

Dosage Forms/Routes:
Tablet/oral;
Capsule/oral;
Solution/oral

Database Search Links:
[PubMed]

[Search PubMed for
Randomized Controlled Trials
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[
PubChem]
[PDSP Ki database]

Initial Approval:
12/30/1993


Manufacturers:

[FDA Search]

Product Insert:
[Link]

RxList:
[Link]

Epocrates:
[Link]

Empirical Formula:
C9H17NO2

Molecular Mass:
171.237 g/mol

Indications:
Gabapentin is indicated as adjunctive therapy in the treatment of partial seizures with and without secondary generalization in patients over 12 years of age with epilepsy. Neurontin is also indicated as adjunctive therapy in the treatment of partial seizures in pediatric patients age 3-12 years.

Gabapentin is also indicated for the management of postherpetic neuralgia in adults.

Possible Mechanisms of Action:
Gabapentin binds to the alpha(2)delta-1 and alpha(2)delta-2 regulatory subunits of voltage-gated calcium channels (33). Gabapentin binds with higher affinity to the alpha(2)delta-1 subunit (33). It does not bind to alpha(2)delta-3 or alpha(2)delta-4 subunits (34). Gabapentin is also an agonist at GABA-B gb1a-gb2 heterodimer receptors (35, 36). In addition, gabapentin exhibits a complex interaction with NMDA receptors (37). The drug may either target certain combinations of NMDA receptor subunits or intracellular processes that affect the phosphorylation states of NMDA receptors (37).

Chemical Class:
structural analog of GABA

PubChem 2D Structure:

Generic Name:
lamotrigine

Trade Name:
Lamictal ® [
GlaxoSmithKline]

IUPAC Name:
6-(2,3-dichlorophenyl)-1,2,4-
triazine-3,5-diamine

Major Metabolite:
lamotrigine 2-N-glucuronide

Dosage Forms/Routes:
Tablet/oral;
Tablet/chewable oral

Database Search Links:
[PubMed]

[Search PubMed for
Randomized Controlled Trials
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[
PubChem]
[PDSP Ki database]

Initial Approval:
12/27/1994


Manufacturers:

[FDA Search]

Product Insert:
[Link]

RxList:
[Link]

Epocrates:
[Link]

Empirical Formula:
C9H7Cl2N5

Molecular Mass:
256.091 g/mol

Indications:
Adjunctive therapy for partial seizures in adults and pediatric patients (>/= 2 years of age); adjunctive therapy for the generalized seizures of Lennox-Gastaut syndrome in adult and pediatric patients (>/= 2 years of age); the maintenance treatment of bipolar I disorder to delay the time to occurrence of mood episodes (depression, mania, hypomania, mixed episodes) in patients treated for acute mood episodes with standard therapy

Possible Mechanisms of Action:
Lamotrigine blocks voltage-gated sodium channels in a use-dependent manner (38). The drug preferentially binds to the channel pore in inactivated but not resting sodium channels; its inhibition of sodium channels is therefore increased by neuronal depolarization (39). Lamotrigine also inhibits N-type and P/Q-type voltage-gated calcium channels (40, 41).

Chemical Class:
phenyltriazine

PubChem 2D Structure:

"3D" Structure (Requires Chime):
[Link]

Generic Name:
levetiracetam

Trade Name:
Keppra ® [UCB]

IUPAC Name:
2-(2-oxopyrrolidin-1-
yl)butanamide

Major Metabolite:
2-pyrrolidone-N-butyric acid

Dosage Forms/Routes:
Tablet/oral;
Solution/oral

Database Search Links:
[PubMed]

[Search PubMed for
Randomized Controlled Trials
]

[
PubChem]
[PDSP Ki database]

Initial Approval:
11/30/1999


Manufacturers:

[FDA Search]

Product Insert:
[Link]

RxList:
[Link]

Epocrates:
[Link]

Empirical Formula:
C8H14N2O2

Molecular Mass:
170.209 g/mol

Indications:
Adjunctive therapy in the treatment of partial onset seizures in adults and children 4 years of age and older with epilepsy

Possible Mechanisms of Action:
Levetiracetam binds to the synaptic vesicle protein SV2A (65).
Levetiracetam may also inhibit N-type calcium channels in a manner that is not related to their activation states (42).

Chemical Class:
pyrrolidine derivative

PubChem 2D Structure:

Generic Name:
lorazepam

Trade Name:
Ativan ® [Baxter]

IUPAC Name:
9-chloro-6-(2-chlorophenyl)-4-
hydroxy-2,5-
diazabicyclo[5.4.0]undeca-
5,8,10,12-tetraen-3-one

Dosage Forms/Routes:
injectable/injection

Major Metabolite:
lorazepam glucuronide

Database Search Links:
[PubMed]

[Search PubMed for
Randomized Controlled Trials
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[
PubChem]
[PDSP Ki database]

Initial Approval:
09/30/1977


Manufacturers:

[FDA Search]

Prescribing Information:
[Link]

RxList:
[Link]


Empirical Formula:
C15H10Cl2N2O2

Molecular Mass:
321.158 g/mol

Indications:
Lorazepam injection is also indicated for the treatment of status epilepticus.

Lorazepam injection is also indicated in adult patients for preanesthetic medication, producing sedation (sleepiness or drowsiness), relief of anxiety, and a decreased ability to recall events related to the day of surgery. It is most useful in those patients who are anxious about their surgical procedure and who would prefer to have diminished recall of the events of the day of surgery.

Possible Mechanism of Action:
Lorazepam is a nonselective benzodiazepine agonist (66).

Chemical Class:
3-hydroxy benzodiazepine

PubChem 2D Structure:

"3D" Structure (Requires Chime):
[
Link]

Generic Name:
oxcarbazepine

Trade Name:
Trileptal ® [Novartis]

Common Chemical Name:
10,11-Dihydro-10-oxo-
5H-dibenz[b,f]azepine-5-
carboxamide

Major Metabolites:
10-hydroxycarbazepine;
10,11-trans-dihydroxy-10,11-
dihydroxycarbamazepine

Dosage Forms/Routes:
Tablet/oral;
Solution/oral

Database Search Links:
[PubMed]

[Search PubMed for
Randomized Controlled Trials
]

[
PubChem]
[PDSP Ki database]

Initial Approval:
01/14/2000


Manufacturers:

[FDA Search]

Product Insert:
[Link]

RxList:
[Link]

Epocrates:
[Link]

Empirical Formula:
C15H12N2O2

Molecular Mass:
252.268 g/mol

Indications:
Monotherapy or adjunctive therapy in the treatment of partial seizures in adults and children ages 4-16 with epilepsy

Possible Mechanisms of Action:
Oxcarbazepine inhibits voltage-gated sodium channels in a use- dependent manner (44). The drug is also a weak inhibitor of L-type calcium channels (45).

Chemical Class:
tricyclic iminostilbene derivative

PubChem 2D Structure:

Generic Name:
phenobarbital

IUPAC Name:
5-ethyl-5-phenyl-1,3-diazinane-
2,4,6-trione

Major Metabolites:
p-hydroxyphenobarbital;
phenobarbital-N-glucoside

Database Search Links:
[PubMed]

[Search PubMed for
Randomized Controlled Trials
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PubChem]
[PDSP Ki database]

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Epocrates:
[Link]

Empirical Formula:
C12H12N2O3

Molecular Mass:
232.235 g/mol

Indications:
Treatment of generalized tonic-clonic and cortical local seizures. And, in the emergency control of certain acute convulsive episodes, e.g., those associated with status epilepticus, cholera, eclampsia, meningitis, tetanus, and toxic reactions to strychnine or local anesthetics.

Phenobarbital is also indicated for the short-term treatment of insomnia and for use as a preanesthetic and sedative.

Possible Mechanisms of Action:
Phenobarbital positively modulates the flow of chloride ions through GABA-A receptor complexes by interacting with the barbiturate binding site (46).

Chemical Class:
barbiturate

PubChem 2D Structure:

"3D" Structure (Requires Chime):
[
Link] 

Generic Name:
phenytoin

Trade Name:
Dilantin ® [Pfizer]

IUPAC Name:
5,5-diphenylimidazolidine-2,4-
dione

Major Metabolite:
5-(p-hydroxyphenyl)-5-
phenylhydantoin

Dosage Forms/Routes:
Suspension/oral;
Tablet/chewable oral

Database Search Links:
[PubMed]

[Search PubMed for
Randomized Controlled Trials
]

[
PubChem]
[PDSP Ki database]

Initial Approval:
01/06/1953


Manufacturers:

[FDA Search]

Product Insert:
[Link] (Supension)

[Link ] (Infatabs)

RxList:
[Link]

Epocrates:
[Link]

Empirical Formula:
C15H12N2O2

Molecular Mass:
252.268 g/mol

Indications:
Suspension: control of tonic-clonic (grand mal) and psychomotor (temporal lobe) seizures

Chewable tablets: control of generalized tonic-clonic (grand mal) and complex partial (psychomotor, temporal lobe) seizures and prevention and treatment of seizures occurring during or following neurosurgery

 

Possible Mechanisms of Action:
Phenytoin inhibits voltage-gated sodium channels in a use- dependent manner (11). Phenytoin is also a low affinity inhibitor at T-type calcium channels that contain the alpha1H subunit (29). In addition, phenytoin inhibits the persistent Na+ current (INaP) (47).

Chemical Class:
hydantoin

PubChem 2D Structure:

"3D" Structure (Requires Chime):
[
Link] 

Generic Name:
phenytoin sodium

Trade Name:
Dilantin ® [Pfizer]

IUPAC Name:
sodium 5-oxo-4,4-diphenyl-1H-
imidazol-2-olate

Major Metabolite:
5-(p-hydroxyphenyl)-5-
phenylhydantoin

Dosage Forms/Routes:
Capsule/oral

Database Search Links:
[PubMed]

[Search PubMed for
Randomized Controlled Trials
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[
PubChem]
[PDSP Ki database]

Initial Approval:
01/06/1953


Manufacturers:

[FDA Search]

Product Insert:
[Link]


RxList:
[Link]

Epocrates:
[Link]

Empirical Formula:
C15H11N2NaO2

Molecular Mass:
274.25 g/mol

Indications:
Control of generalized tonic-clonic (grand mal) and complex partial (psychomotor, temporal lobe) seizures and prevention and treatment of seizures occurring during or following neurosurgery

Possible Mechanisms of Action:
Phenytoin inhibits voltage-gated sodium channels in a use- dependent manner (11). Phenytoin is also a low affinity inhibitor at T-type calcium channels that contain the alpha1H subunit (29). In addition, phenytoin inhibits the persistent Na+ current (INaP) (47).

Chemical Class:
hydantoin

PubChem 2D Structure:

"3D" Structure (Requires Chime):
[
Link]

Generic Name:
pregabalin

Trade Name:
Lyrica ® [Pfizer]

IUPAC Name:
3-(aminomethyl)-5-methyl-
hexanoic acid

Major Metabolite:
pregabalin is excreted primarily unchanged in urine

Dosage Forms/Routes:
Capsule/oral

Database Search Links:
[PubMed]

[Search PubMed for
Randomized Controlled Trials
]

[
PubChem]
[PDSP Ki database]

Initial Approval:
12/30/2004


Manufacturers:

[FDA Search]

RxList:
[Link]

Epocrates:
[Link]

Empirical Formula:
C8H17NO2

Molecular Mass:
159.226 g/mol

Indications:
Adjunctive therapy in the treatment of partial seizures in adults; neuropathic pain associated with diabetic peripheral neuropathy; postherpetic neuralgia

Possible Mechanisms of Action:
Pregabalin binds to the alpha(2)delta-1 and alpha(2)delta-2 regulatory subunits of voltage-gated calcium channels (48). Pregabalin binds with higher affinity to the alpha(2)delta-2 subunit (48).

Chemical Class:
structural analog of GABA

PubChem 2D Structure:

Generic Name:
primidone

Trade Name:
Mysoline ® [Valeant]

IUPAC Name:
5-ethyl-5-phenyl-1,3-diazinane-
4,6-dione

Major Metabolites:
phenobarbital;
phenylethylmalonamide

Dosage Forms/Routes:
Tablet/oral

Database Search Links:
[PubMed]

[Search PubMed for
Randomized Controlled Trials
]

[
PubChem]
[PDSP Ki database]

Initial Approval:
03/08/1954


Manufacturers:

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Empirical Formula:
C12H14N2O2

Molecular Mass:
218.252 g/mol

Indications:
Primidone, either alone or used concomitantly with other antiepileptic drugs, is indicated in the control of grand mal, psychomotor, and focal epileptic seizures. It may control grand mal seizures refractory to other antiepileptic therapy.

Possible Mechanisms of Action:
The mechanisms of action of primidone and one of its active metabolites, phenylethylmalonamide, have not been well defined. Phenobarbital, another active metabolite of primidone, positively modulates the flow of chloride ions through GABA-A receptor complexes by interacting with the barbiturate binding site (46).

Chemical Class:
desoxybarbiturate

PubChem 2D Structure:

Generic Name:
tiagabine hydrochloride

Trade Name:
Gabitril ® [Cephalon]

IUPAC Name:
1-[4,4-bis(3-methylthiophen-2-
yl)but-3-enyl]piperidine-3-
carboxylic acid hydrochloride

Major Metabolites:
5-oxo-tiagabine

Dosage Forms/Routes:
Tablet/oral

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PubChem]
[PDSP Ki database]

Initial Approval:
09/30/1997


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Empirical Formula:
C20H26ClNO2S2

Molecular Mass:
412.011 g/mol

Indications:
Adjunctive therapy in adults and children 12 years and older in the treatment of partial seizures

Possible Mechanisms of Action:
Tiagabine inhibits the GABA reuptake transporter (49).

Chemical Class:
nipecotic acid derivative

PubChem 2D Structure:

Generic Name:
topiramate

Trade Name:
Topamax ® [Ortho-McNeil]

Common Chemical Name:
2,3:4,5-Di-O-isopropylidene-
β-D-fructopyranose sulfamate

Major Metabolites:
2,3-O-des-isopropylidene-
topiramate;
10-hydroxy-topiramate

Dosage Forms/Routes:
Tablet/oral;
Capsule/oral

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Initial Approval:
12/24/1996


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Empirical Formula:
C12H21NO8S

Molecular Mass:
339.363 g/mol

Indications:
Topiramate is indicated for initial monotherapy in patients 10 years of age and older with partial onset or primary generalized tonic-clonic seizures; adjunctive therapy for adults and pediatric patients ages 2-16 years with partial onset seizures or primary generalized tonic-clonic seizures; adjunctive therapy for patients 2 years of age and older with seizures associated with Lennox-Gastaut syndrome; and prophylaxis of migraine for adults

Possible Mechanisms of Action:
Topiramate inhibits carbonic anhydrase isozymes such as CA II (50), CA IV (50, 51), and CA V (52). Topiramate has also been shown to inhibit both the fast and persistent components of sodium currents in neocortical cells (53). In addition, the drug may inhibit L-type calcium channels (54, 55). Topiramate also inhibits inward currents at some subtypes of kainate and AMPA glutamate receptors (56, 57). Finally, the drug may act as a histone deacetylase inhibitor (64).

Chemical Class:
sulfamated monosaccharide

PubChem 2D Structure:

"3D" Structure (Requires Chime):
[Link]

Generic Name:
trimethadione

Trade Name:
Tridione ® [Abbott Labs]

IUPAC Name:
3,5,5-trimethyloxazolidine-2,4-
dione

Major Metabolites:
dimethadione

Dosage Forms/Routes:
Tablet/oral

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Initial Approval:
01/25/1946


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Empirical Formula:
C6H9NO3

Molecular Mass:
143.141 g/mol

Indications:
Control of absence (petit mal) seizures that are refractory to treatment with other medications. Trimethadione should not be used unless other less toxic antiepileptic drugs have been ineffective in controlling seizures.

Possible Mechanisms of Action:
Trimethadione and its active metabolite, dimethadione, are T-type calcium channel inhibitors (58).

Chemical Class:
oxazolidinedione derivative

PubChem 2D Structure:

"3D" Structure (Requires Chime):
[
Link]

Generic Name:
valproic acid

Trade Name:
Depakene ® [Abbott Labs]

IUPAC Name:
2-propylpentanoic acid

Major Metabolites:
3-keto-valproic acid;
trans-2-ene valproic acid; valproic acid glucuronide

Dosage Forms/Routes:
Capsule/oral;
Syrup/oral

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[PDSP Ki database]

Initial Approval:
02/28/1978


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Empirical Formula:
C8H16O2

Molecular Mass:
144.211 g/mol

Indications:
Sole and adjunctive therapy in the treatment of simple and complex absence seizures; adjunctive therapy in patients with multiple seizure types which include absence seizures

Possible Mechanisms of Action:
Valproic acid is a histone deacetylase inhibitor (20). The enhancement of gamma-aminobutyric acid (GABA) activity by valproic acid is possibly due to the downregulation of GAT-1 and GAT-3 GABA transporter proteins by the drug (21); the cause of this effect is currently unknown. Valproic acid also inhibits succinate semialdehyde dehydrogenase (22).
At voltage-gated sodium channnels, valproic acid shifts the voltage dependence of steady-state inactivation to more hyperpolarized potentials (23); the degree to which this action occurs at therapeutically relevant concentrations in humans is currently not known (24). Finally, valproic acid may inhibit T-type calcium channels (25).

Chemical Class:
carboxylic acid derivative

PubChem 2D Structure:


"3D" Structure (Requires Chime):
[Link] 

Generic Name:
zonisamide

Trade Name:
Zonegran ® [Dainippon]

IUPAC Name:
benzo[d]isoxazol-3-
ylmethanesulfonamide

Major Metabolites:
N-acetylzonisamide;
2-sulfamoylacetylphenol

Dosage Forms/Routes:
Capsule/oral

Database Search Links:
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Initial Approval:
03/27/2000


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Empirical Formula:
C8H8N2O3S

Molecular Mass:
212.227 g/mol

Indications:
Adjunctive therapy in the treatment of partial seizures in adults with epilepsy

Possible Mechanisms of Action:
Zonisamide inhibits voltage-gated sodium channels when action potentials are occuring at a high frequency (59). The drug also inhibits T-type calcium channels (60, 61). Zonisamide may also inhibit carbonic anhydrase isoenzymes such as CA II (52), CA V (52), and CA IX (62).

Chemical Class:
methanesulfonamide

PubChem 2D Structure:

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