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Vigabatrin
Systematic (IUPAC) name
4-aminohex-5-enoic acid
Identifiers
CAS number	60643-86-9
ATC code	N03AG04
PubChem	5665
DrugBank	APRD00282
Chemical data
Formula	C6H11NO2
Mol. mass	129.157 g/mol
Pharmacokinetic data
Bioavailability	80-90%
Protein binding	0
Metabolism	Almost no metabolic transformation occurs
Half life	5-8 hours in young adults, 12-13 hours in the elderly.
Excretion	Renal
Therapeutic considerations
Pregnancy cat.	?
Legal status	Not a controlled substance
Routes	Oral

Vigabatrin is an anticonvulsant that inhibits the catabolism of GABA. It is an analog of GABA, but it is not a receptor agonist.^[1]

Contents 1 Mechanism of action 2 Pharmacokinetics 3 Uses 3.1 Approved/clinically proven 3.1.1 Canada 3.1.2 Mexico 3.2 Unapproved/Investigational 4 Adverse effects 4.1 Central nervous system 4.1.1 Common 4.1.2 Rare 4.2 Gastrointestinal 4.2.1 Common 4.2.2 Rare 4.3 Body as a Whole 4.3.1 Common 4.4 Teratogenicity 4.5 More on "abnormal vision" 5 Drug interactions 6 Brand names 7 References and end notes

Vigabatrin is an irreversible inhibitor of gamma-aminobutyric acid transaminase (GABA-T), the enzyme responsible for the catabolism of GABA, which increases the level of GABA in the synapses.^[1]

Vigabatrin is a racemic compound, and its [S]-enantiomer is pharmacologically active.^[2],[3]

With most drugs, elimination half-life is a useful predictor of dosing schedules and the time needed to reach steady state concentrations. In the case of vigabatrin, however, it has been found that the half-life of biologic activity is far longer than the elimination half-life.^[4]

For vigabatrin, there is no range of target concentrations because researchers found no difference between the serum concentration levels of responders and those of non-responders.^[5] Instead, the duration of action is believed to be more a function of the GABA-T resynthesis rate; levels of GABA-T do not usually return to their normal state until six days after stopping the medication.^[3]

In Canada, vigabatrin is approved for use as an adjunctive treatment (with other drugs) in treatment resistant epilepsy, complex partial seizures, secondary generalized seizures, and for monotherapy use in infantile spasms in West syndrome.^[1]

As of 2003, vigabatrin is approved in Mexico for the treatment of epilepsy that is not satisfactorily controlled by conventional therapy (adjunctive or monotherapy) or in recently diagnosed patients who have not tried other agents (monotherapy).^[6]

Vigabatrin is also indicated for monotherapy use in secondarily generalized tonic-clonic seizures, partial seizures, and in infantile spasms due to West syndrome.^[6]

In November of 2001, a team of scientists lead by Peter Zwanzger of the University of Munich reported that vigabatrin reduced cholecystokinin tetrapeptide-induced symptoms of panic disorder, in addition to elevated cortisol and ACTH levels, in healthy volunteers.^[7]

In 1994, Feucht and Brantner-Inthaler reported that vigabatrin reduced seizures by 50-100% in 85% of children with Lennox-Gastaut syndrome who had poor results with a valproate.^[8]

In 1984, a double-blind crossover-study of six Huntington's disease patients—five of them on antipsychotics—reported that vigabatrin did little, if anything, to improve hyperkinetic movements, the ability to carry out daily activities, or normalize motor function.^[9]

Out of 2,081 subjects, somnolence (12.5%), headache (3.8%), dizziness (3.8%), nervousness (2.7%), depression (2.5%), memory disturbances (2.3%), diplopia (2.2%), aggression (2.0%), ataxia (1.9%), vertigo (1.9%), hyperactivity (1.8%), vision abnormalities (1.6%), confusion (1.4%), insomnia (1.3%), impaired concentration (1.2%), personality disorder (1.1%).^[1] Out of 299 children, 33 (11%) became hyperactive.^[1]

Some patients develop psychosis during the course of vigabatrin therapy,^[10] which is more common in adults than in children.^[11] This can happen even in patients with no prior history of psychosis.^[12] Other rare CNS side effects include anxiety, emotional lability, irritability, tremor, abnormal gait, and speech disorder.^[1]

Abdominal pain (1.6%), constipation (1.4%), vomiting (1.4%), and nausea (1.4%).^[1]

Dyspepsia and increased appetite occurred in less than 1% of subjects in clinical trials.^[1]

Fatigue (9.2%), weight gain (5.0%), asthenia (1.1%).^[1]

A teratology study conducted in rabbits found that a dose of 150mg/kg/day caused cleft palate in 2% of pups and a dose of 200 mg/kg/day caused it in 9%.^[1] This may be due to a decrease in methionine levels, according to a study published in March of 2001.^[13] In 2005, a study conducted at the University of Catania was published stating that rats whose mothers had consumed 250-1000 mg/kg/day had poorer performance in the water maze and open-field tasks, rats in the 750-mg group were underweight at birth and did not catch up to the control group, and rats in the 1000 mg group did not survive pregnancy.^[14]

There is no controlled teratology data in humans to date.

In 2003, vigabatrin was shown by Frisén and Malmgren to cause irreversible diffuse atrophy of the retinal nerve fiber layer in a retrospective study of 25 patients.^[15] This has the most effect on the outer area (as opposed to the macular, or central area) of the retina.^[16]

A study published in 2002 found that vigabatrin causes a statistically significant increase in plasma clearance of carbamazepine.^[17]

In 1984, Drs Rimmer and Richens at the University of Wales reported that administering vigabatrin with phenytoin lowered the serum phenytoin concentration in patients with treatment-resistant epilepsy.^[18] The concentration of phenytoin falls to 23% within five weeks, according to an experiment published in 1989 by the same two scientists that tried and failed to elucidate the mechanism behind this interaction.^[19]

Vigabatrin is sold as Sabril® in Canada,^[20] Mexico,^[6] and the United Kingdom.^[21] The brand name in Denmark is Sabrilex®.