The anticonvulsants, also called antiepileptic drugs (abbreviated "AEDs"), belong to a diverse group of pharmaceuticals used in prevention of the occurrence of epileptic seizures. Pharmacology (from Greek grc φάρμακον pharmakon, "drug" and grc -λογία -logia) is the study of how Drugs Epilepsy is a common chronic Neurological disorder that is characterized by recurrent unprovoked seizures. An epileptic seizure is caused by excessive and/or hypersynchronous electrical Neuronal activity and is usually self-limiting Anticonvulsants are also increasingly finding ways into the treatment of bipolar disorder, since many seem to act as mood stabilizers. This article refers to the medication For other uses see Stabilizer. The goal of an anticonvulsant is to suppress the rapid and excessive firing of neurons that start a seizure. Neurons (ˈnjuːɹɒn also known as neurones and nerve cells) are responsive cells in the Nervous system that process and transmit information Failing this, a good anticonvulsant would prevent the spread of the seizure within the brain and offer protection against possible excitotoxic effects that may result in brain damage. Excitotoxicity is the pathological process by which nerve cells are damaged and killed by glutamate and similar substances Brain damage, or Acquired brain injury, is the destruction or degeneration of Brain cells. However, anticonvulsants themselves have been linked to lowered IQ. ^[1]

The major molecular targets of marketed anticonvulsant drugs are voltage-gated sodium channels; components of the GABA system, including GABA_A receptors, the GAT-1 GABA transporter, and GABA transaminase; and voltage-gated calcium channels. Gamma-aminobutyric acid (GABA is the chief inhibitory Neurotransmitter in the Mammalian Central nervous system. 4-aminobutyrate aminotransferase (or GABA transaminase) is an enzyme which catalyzes the conversion of 4-aminobutanoic acid (GABA and 2-oxoglutarate into A Calcium channel is an Ion channel which displays selective permeabiltiy to Calcium ions ^[2]

Some anticonvulsants have shown antiepileptogenic effects in animal models of epilepsy. That is, they either prevent the expected development of epilepsy or can halt or reverse the progression of epilepsy. However, no drug has shown this effect in human trials. ^[3]

Contents 1 Approval 2 Drugs 2.1 Aldehydes 2.2 Aromatic allylic alcohols 2.3 Barbiturates 2.4 Benzodiazepines 2.5 Bromides 2.6 Carbamates 2.7 Carboxamides 2.8 Fatty acids 2.9 Fructose derivatives 2.10 Gaba analogs 2.11 Hydantoins 2.12 Oxazolidinediones 2.13 Propionates 2.14 Pyrimidinediones 2.15 Pyrrolidines 2.16 Succinimides 2.17 Sulfonamides 2.18 Triazines 2.19 Ureas 2.20 Valproylamides (amide derivatives of valproate) 3 Diet 4 Devices 5 Marketing approval history 6 See also 7 References 8 External links

Approval

The usual method of achieving approval for a drug is to show it is effective when compared against placebo, or that it is more effective than an existing drug. In monotherapy (where only one drug is taken) it is considered unethical by most to conduct a trial with placebo on a new drug of uncertain efficacy. This is because untreated epilepsy leaves the patient at significant risk of death. Therefore, almost all new epilepsy drugs are initially approved only as adjunctive (add-on) therapies. Patients whose epilepsy is currently uncontrolled by their medication (i. e. , it is refractory to treatment) are selected to see if supplementing the medication with the new drug leads to an improvement in seizure control. Any reduction in the frequency of seizures is compared against a placebo. ^[3]

Once there is confidence that a drug is likely to be effective in monotherapy, trials are conducted where the drug is compared to an existing standard. For partial-onset seizures, this is typically carbamazepine. Carbamazepine ("CBZ" is an Anticonvulsant and mood stabilizing drug used primarily in the treatment of Epilepsy and Bipolar disorder Despite the launch of over ten drugs since 1990, no new drug has been shown to be more effective than the older set, which includes carbamazepine, valproate and phenytoin. The lack of superiority over existing treatment, combined with the lack of placebo-controlled trials, means that few modern drugs have earned FDA approval as initial monotherapy. In contrast, Europe only requires equivalence to existing treatments, and has approved many more. Despite their lack of FDA approval, the American Academy of Neurology and the American Epilepsy Society still recommend a number of these new drugs as initial monotherapy. The American Academy of Neurology (AAN is a professional society for neurologists and neuroscientists ^[3]

Drugs

In the following list, the dates in parentheses are the earliest approved use of the drug.

Aldehydes

Main article: Aldehydes

• Paraldehyde (1882). An aldehyde is an organic compound containing a terminal Carbonyl group. Paraldehyde is the cyclic form of three Acetaldehyde molecules (a trimer One of the earliest anticonvulsants. Still used to treat status epilepticus, particularly where there are no resuscitation facilities. Status epilepticus (SE refers to a life-threatening condition in which the Brain is in a state of persistent Seizure.

Aromatic allylic alcohols

• Stiripentol (2001 - limited availability). Stiripentol (marketed as Diacomit by Laboratoires BIOCODEX is an Anticonvulsant drug used in the treatment of Epilepsy. Indicated for the treatment of severe myoclonic epilepsy in infancy (SMEI). Myoclonus (maɪˈɒklənəs is brief involuntary twitching of a Muscle or a group of muscles

Barbiturates

Main article: Barbiturates

Barbiturates are drugs that act as central nervous system (CNS) depressants, and by virtue of this they produce a wide spectrum of effects, from mild sedation to anesthesia. Barbiturates are drugs that act as central nervous system Depressants and by virtue of this they produce a wide spectrum of effects from mild Sedation Barbiturates are drugs that act as central nervous system Depressants and by virtue of this they produce a wide spectrum of effects from mild Sedation Medication, also referred to as medicine, can be loosely defined as any substance intended for use in the diagnosis cure mitigation treatment or prevention of disease Depressant is a chemical agent that diminishes the function or activity of a specific part of the body (see also Sedative) Sedation is a Medical procedure involving the administration of Sedative drugs generally to facilitate a medical procedure with Local anaesthesia. Anesthesia, or anaesthesia (see spelling differences; from Greek grc αν- an-, "without" and grc αἲσθησις The following are classified as anticonvulsants:

• Phenobarbital (1912). A section of the Anatomical Therapeutic Chemical Classification System. Phenobarbital ( INN) or phenobarbitone (former BAN) is a Barbiturate, first marketed as Luminal by Friedr See also the related drug primidone. Primidone is an Anticonvulsant of the Pyrimidinedione class whose active Metabolites Phenobarbital (major and phenylethylmalonamide (PEMA (minor
• Methylphenobarbital (1935). Methylphenobarbital, also known as mephobarbital, (marketed in the US under the brand name Mebaral by Ovation) is a drug which is a Barbiturate Known as mephobarbital in the US. No longer marketed in the UK
• Metharbital (1952). Metharbital was patented in 1905 by Emil Fischer working for Merck. No longer marketed in the UK or US.
• Barbexaclone (1982). Barbexaclone (marketed in Italy as Maliasin by Abbott Laboratories) is a salt compound of Phenobarbital and Propylhexedrine. Only available in some European countries.

Phenobarbital was the main anticonvulsant from 1912 till the development of phenytoin in 1938. Today, phenobarbital is rarely used to treat epilepsy in new patients since there are other effective drugs that are less sedating. Phenobarbital sodium injection can be used to stop acute convulsions or status epilepticus, but a benzodiazepine such as lorazepam, diazepam or midazolam is usually tried first. Status epilepticus (SE refers to a life-threatening condition in which the Brain is in a state of persistent Seizure. Other barbiturates only have an anticonvulsant effect at anaesthetic doses.

Benzodiazepines

Main article: Benzodiazepines

The benzodiazepines are a class of drugs with hypnotic, anxiolytic, anticonvulsive, amnestic and muscle relaxant properties. The benzodiazepines (pronounced, often abbreviated to "benzos") are a class of Psychoactive drugs with varying Hypnotic Medication, also referred to as medicine, can be loosely defined as any substance intended for use in the diagnosis cure mitigation treatment or prevention of disease For the state of mind see Hypnosis. Hypnotic drugs induce Sleep (which differentiates them from the Sedative An anxiolytic is a drug prescribed for the treatment of Symptoms of Anxiety. Amnesia (from Greek) is a condition in which Memory is disturbed This article refers to skeletal muscle relaxants For information on Smooth muscle relaxants see Antispasmodic. Benzodiazepines act as a central nervous system depressant. The relative strength of each of these properties in any given benzodiazepine varies greatly and influences the indications for which it is prescribed. Long-term use can be problematic due to the development of tolerance and dependency. Drug tolerance occurs when a subject's reaction to a Psychoactive drug (such as a painkiller or intoxicant decreases so that larger doses are required to achieve the same effect The term " addiction " is used in many contexts to describe an obsession compulsion or excessive Physical dependence or psychological dependence such as Of the many drugs in this class, only a few are used to treat epilepsy:

• Clobazam (1979). Clobazam is a drug which is a Benzodiazepine derivative It has been marketed as an Anxiolytic since 1975 and an Anticonvulsant since 1984 Notably used on a short-term basis around menstruation in women with catamenial epilepsy.
• Clonazepam (1974). Clonazepam (marketed by Roche under the trade-names Klonopin in the United States and Rivotril, Ravotril or Rivatril in Europe South
• Clorazepate (1972). Clorazepate (marketed under the brand names Tranxene and Tranxilium) is a drug which is a Benzodiazepine

The following benzodiazepines are used to treat status epilepticus:

• Diazepam (1963). Status epilepticus (SE refers to a life-threatening condition in which the Brain is in a state of persistent Seizure. Diazepam (daɪˈæzɨpæm first marketed as Valium by Hoffmann-La Roche, is a Benzodiazepine derivative Drug. Can be given rectally by trained care-givers.
• Midazolam (N/A). Midazolam (marketed under brand names Dormicum, Flormidal, Versed, Hypnovel and Dormonid, pronounced mɪˈdæzəlæm Increasingly being used as an alternative to diazepam. This water-soluble drug is squirted into the side of the mouth but not swallowed. It is rapidly absorbed by the buccal mucosa. Buccal mucosa is Mucous membrane of the inside of the Cheek. It is non-keratinised and is continuous with the mucosae of the soft palate under surface of tongue and
• Lorazepam (1972). Lorazepam (also known by its brand name Ativan or Temesta) is a Benzodiazepine drug with short to medium duration of action Given by injection in hospital.

Nitrazepam, temazepam, and especially nimetazepam are powerful anticonvulsant agents, however their use is rare due to an increased incidence of side effects and strong sedative and motor-impairing properties. Nitrazepam is a type of Benzodiazepine drug It is a hypnotic drug with Sedative and motor impairing properties Anxiolytic, Amnestic Temazepam (marketed under brand names Restoril, Euhypnos, Normison, Remestan, Tenox and Norkotral) is an intermediate-acting Nimetazepam (marketed under brand name Erimin) is a powerful Hypnotic drug which is a Benzodiazepine derivative which was first synthesized in Japan

Bromides

Main article: Bromides

• Potassium bromide (1857). A bromide Ion is a Bromine atom with charge of −1 Compounds with bromine in formal Oxidation state −1 are called bromides Potassium bromide ( K[[Bromine Br]] is a salt, widely used as an Anticonvulsant and a Sedative in the late 19th and early 20th centuries The earliest effective treatment for epilepsy. There would not be a better drug for epilepsy until phenobarbital in 1912. It is still used as an anticonvulsant for dogs and cats.

Carbamates

Main article: Carbamates

• Felbamate (1993). Carbamates, or Urethanes are a group of Organic compounds sharing a common Functional group with the general structure -NH(COO- Felbamate (marketed under the brand name Felbatol by MedPointe) is an Anticonvulsant drug used in the treatment of Epilepsy. This effective anticonvulsant has had its usage severely restricted due to rare but life-threatening side effects.

Carboxamides

Main article: Carboxamides

The following are carboxamides:

• Carbamazepine (1963). Carboxamides are drugs that can be used as Anticonvulsants. In Organic chemistry carboxamides (or Amino Carbonyls are Functional Carbamazepine ("CBZ" is an Anticonvulsant and mood stabilizing drug used primarily in the treatment of Epilepsy and Bipolar disorder A popular anticonvulsant that is available in generic formulations.
• Oxcarbazepine (1990). Oxcarbazepine (marketed as Trileptal by Novartis or Trexapin by Taro is an Anticonvulsant and mood stabilizing drug, used primarily A derivative of carbamazepine that has similar efficacy but is better tolerated.

Fatty acids

Main article: Fatty acids

The following are fatty-acids:

• The valproates — valproic acid, sodium valproate, and divalproex sodium (1967). In Chemistry, especially Biochemistry, a fatty acid is a Carboxylic acid often with a long unbranched Aliphatic tail ( chain) which Valproic acid ( VPA) is a Chemical compound that has found clinical use as an Anticonvulsant and mood-stabilizing drug, primarily in Valproic acid ( VPA) is a Chemical compound that has found clinical use as an Anticonvulsant and mood-stabilizing drug, primarily in See also Valproic acid Sodium valproate ( INN) or valproate sodium ( USAN) is the sodium salt of Valproic acid and is an See also Valproic acid Valproate semisodium ( INN) or divalproex sodium ( USAN) consists of a compound of Sodium valproate and
• Vigabatrin (1989). Vigabatrin is an Anticonvulsant that inhibits the Catabolism of GABA.
• Progabide
• Tiagabine (1996). Progabide ( INN) (trade name Gabrene, Sanofi-Synthelabo) is an analog and Prodrug of Gamma-aminobutyric acid used in the Tiagabine (taɪˈæɡəbiːn] is an anti-convulsive

Vigabatrin and progabide are also analogs of GABA.

Fructose derivatives

Main article: Fructose

• Topiramate (1995). Fructose (also levulose or laevulose) is a simple reducing Sugar ( Monosaccharide) found in many foods and is one of the three Topiramate (brand name Topamax) is an Anticonvulsant drug produced by Ortho-McNeil Neurologics and Noramco Inc

Gaba analogs

• Gabapentin (1993). Gabapentin (brand name Neurontin) is a medication originally developed for the treatment of Epilepsy.
• Pregabalin (2004). Pregabalin ( INN) (prɨˈgæbəlɨn is an Anticonvulsant drug used for Neuropathic pain and as an adjunct therapy for Partial seizures with or

Hydantoins

Main article: Hydantoins

The following are hydantoins:

• Ethotoin (1957). Hydantoin, which is also known as glycolylurea, is a Heterocyclic Organic compound that can be thought of as a cyclic "double- Condensation reaction Ethotoin (marketed as Peganone by Ovation) is an Anticonvulsant drug used in the treatment of Epilepsy.
• Phenytoin (1938). Phenytoin sodium is a commonly used Antiepileptic. Phenytoin acts to dampen the unwanted runaway brain activity seen in seizure by reducing electrical conductance among brain
• Mephenytoin
• Fosphenytoin (1996). Mephenytoin (marketed as Mesantoin by Novartis is a Hydantoin, Fosphenytoin ( Cerebyx, Parke-Davis; Prodilantin, Pfizer Holding France) is a water-soluble Phenytoin Prodrug used only

Oxazolidinediones

Main article: Oxazolidinediones

The following are oxazolidinediones:

• Paramethadione
• Trimethadione (1946). The following are oxazolidinediones Paramethadione Trimethadione Ethadione to chemicals for scientifical Paramethadione is an Anticonvulsant in the Oxazolidinedione class Trimethadione is an Oxazolidinedione Anticonvulsant. It is used to treat Epileptic conditions that are resistant to other treatments recent studies by
• Ethadione

Propionates

Main article: Propionates

• Beclamide

Pyrimidinediones

Main article: Pyrimidinediones

• Primidone (1952). Ethadione is an Anticonvulsant medication in the Oxazolidinedione family The propionate ( IUPAC name propanoate) Ion is C 2 H 5C OO sup>&minus ( Propionic acid Beclamide (marketed as Chloracon, Hibicon, Posedrine, Nydrane, Seclar, and other names is a Propionate and was used as Pyrimidinediones are a class of chemical compounds characterized by a Pyrimidine ring subsubstituted with two Carbonyl groups Primidone is an Anticonvulsant of the Pyrimidinedione class whose active Metabolites Phenobarbital (major and phenylethylmalonamide (PEMA (minor

Pyrrolidines

Main article: Pyrrolidines

• Brivaracetam
• Levetiracetam (1999). Pyrrolidine, also known as tetrahydropyrrole, is an Organic compound with the molecular formula C4H9N Brivaracetam, the 4-n-propyl analog of Levetiracetam, is a Racetam derivative with Anticonvulsant properties Levetiracetam ( INN) (lɛvɨtɪˈræsɨtæm
• Seletracetam

Succinimides

Main article: Succinimides

The following are succinimides:

• Ethosuximide (1955). Seletracetam is a Drug of the Racetam family It is currently being developed by UCB Pharmaceuticals as an Anticonvulsant drug Succinimide is a cyclic Imide with the formula C4H5NO2 It appears as a white or colorless crystalline solid and has a faint odor of sweat Ethosuximide is a Succinimide Anticonvulsant, used mainly in Absence seizures Uses Approved It is approved for absence
• Phensuximide
• Mesuximide

Sulfonamides

Main article: Sulfonamides

• Acetazolamide (1953). Phensuximide is an Anticonvulsant in the Succinimide class Mesuximide (or methsuximide) is an Anticonvulsant medication It is sold by Pfizer under the tradenames Petinutin (Switzerland and Celontin There are several sulfonamide-based groups of drugs The original antibacterial sulfonamides (sometimes called simply sulfa drugs are synthetic antimicrobial agents that contain the sulfonamide Acetazolamide, sold under the trade name Diamox, is a Carbonic anhydrase inhibitor that is used to treat Glaucoma, Epileptic seizures Benign
• Sulthiame
• Methazolamide
• Zonisamide (2000). Sultiame ( rINN, also known as sulthiame) is a Sulfonamide and Inhibitor of the Enzyme carbonic anhydrase. Methazolamide ( Neptazane) is a Carbonic anhydrase inhibitor Zonisamide is a Sulfonamide Anticonvulsant approved for use as an adjunctive therapy in adults with partial-onset seizures History

Triazines

Main article: Triazines

• Lamotrigine (1990). A triazine is one of three Organic chemicals Isomeric with each other whose Empirical formula is 333 Lamotrigine (marketed as Lamictal (ləˈmɪktəl by GlaxoSmithKline, called Lamictin in South Africa, he למוג'ין ( Lamogine

Ureas

Main article: Ureas

• Pheneturide
• Phenacemide

Valproylamides (amide derivatives of valproate)

Main article: Amides

• Valpromide
• Valnoctamide

Diet

The ketogenic diet is a strict medically supervised diet that has an anticonvulsant effect. Urea is an Organic compound with the Chemical formula ( N[[hydrogen H]]22 C[[oxygen O]] Pheneturide (or ethylphenacemide) is an Anticonvulsant medication Phenacemide is an Anticonvulsant of the Urea class In Chemistry, an amide is one of three kinds of Compounds (sometimes called acid amide the organic Functional group characterized Valpromide (marketed as Depamide by Sanofi-aventis) is a Carboxamide derivative of Valproic acid used in the treatment of Epilepsy Valnoctamide ( INN, USAN) has been used in France as an Sedative - Hypnotic since 1964 The ketogenic diet is a high fat adequate Protein, low carbohydrate diet, primarily used to treat difficult-to-control (refractory Epilepsy in children It is typically used in children with refractory epilepsy.

Devices

The vagus nerve stimulator (VNS) is a device that sends electric impulses to the left vagus nerve in the neck via a lead implanted under the skin. Vagus nerve stimulation (VNS is an adjunctive treatment for certain types of intractable Epilepsy and major depression. The vagus nerve (ˈveɪˌgəs (VĀ-gəs (also called pneumogastric nerve or cranial nerve X) is the tenth of twelve paired Cranial nerves, and is the It was FDA approved in 1997 as an adjunctive therapy for partial-onset epilepsy.

Marketing approval history

The following table lists anticonvulsant drugs together with the date their marketing was approved in the US, UK and France. Data for the UK and France is incomplete. In recent years, the European Medicines Agency has approved drugs throughout the European Union. The European Medicines Agency ( EMEA) is a European agency for the evaluation of medicinal products. The European Union ( EU) is a political and economic union of twenty-seven member states, located primarily in Some of the drugs are no longer marketed.

Drug	Brand	US	UK	France
acetazolamide	Diamox	1953-07-271953-07-27[4]	1988[5]
carbamazepine	Tegretol	1974-07-151974-07-15[6][7]	1965[5]	1963[8]
clobazam	Frisium		1979[5]
clonazepam	Klonopin/Rivotril	1975-06-041975-06-04[9]	1974[5]
diazepam	Valium	1963-11-151963-11-15[10]
divalproex sodium	Depakote	1983-03-101983-03-10[11]
ethosuximide	Zarontin	1960-11-021960-11-02[12]	1955[5]	1962[8]
ethotoin	Peganone	1957-04-221957-04-22[13]
felbamate	Felbatol	1993-07-291993-07-29[14]
fosphenytoin	Cerebyx	1996-08-051996-08-05[15]
gabapentin	Neurontin	1993-12-301993-12-30[16]	1993-05May 1993[5][8]	1994-10October 1994[8]
lamotrigine	Lamictal	1994-12-271994-12-27[17]	1991-10October 1991[5][8]	1995-05May 1995[8]
levetiracetam	Keppra	1999-11-301999-11-30[18]	2000-09-292000-09-29[5][19]	2000-09-292000-09-29[19]
mephenytoin	Mesantoin	1946-10-231946-10-23[20]
metharbital	Gemonil	1952[21][22]
methsuximide	Celontin	1957-02-081957-02-08[23]
methazolamide	Neptazane	1959-01-261959-01-26[24]
oxcarbazepine	Trileptal	2000-01-142000-01-14[25]	2000[5]
phenobarbital			1912[5]	1920[8]
phenytoin	Dilantin/Epanutin	1938[26][8]	1938[5]	1941[8]
phensuximide	Milontin	1953[27][28]
pregabalin	Lyrica	2004-12-302004-12-30[29]	2004-07-062004-07-06[5][30]	2004-07-062004-07-06[30]
primidone	Mysoline	1954-03-081954-03-08[31]	1952[5]	1953[8]
sodium valproate	Epilim		1977-12December 1977[8]	1967-06June 1967[8]
stiripentol	Diacomit		2001-12-052001-12-05[32]	2001-12-052001-12-05[32]
tiagabine	Gabitril	1997-09-301997-09-30[33]	1998[5]	1997-11November 1997[8]
topiramate	Topamax	1996-12-241996-12-24[34]	1995[5]
trimethadione	Tridione	1946-01-251946-01-25[35]
valproic acid	Depakene/Convulex	1978-02-281978-02-28[36]	1993[5]
vigabatrin	Sabril		1989[5]
zonisamide	Zonegran	2000-03-272000-03-27[37]	2005-03-102005-03-10[5][38]	2005-03-102005-03-10[38]

See also

• ATC code N03

References

• Drug Reference for FDA Approved Epilepsy Drugs
• Epilepsy Action: UK Anti-Epileptic Drugs List

External links

• eMedicine: Antiepileptic Drugs: an overview
• NINDS: Anticonvulsant Screening Program
• Use of Anticonvulsants in Pharmacotherapy of Bronchial Asthma
• MDNG: Anticonvulsants and Bone Health

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