Vigabatrin anticonvulsant

Vigabatrin has an unacceptable adverse effect profile, but consistent findings in animal studies suggest that GABA agonists deserve further study. a-AMPA antagonism, or antikindling action, may also be important for some anticonvulsants. 

Anticonvulsants (barbiturates, including phenobar-bital and primidone carbamazepine felbamate phenytoin topiramate vigabatrin)... 

Changes in body weight associated with anticonvulsants have been reviewed (116), including the effects of the antiepileptic drugs that have been most commonly associated with this adverse effect (valproic acid, carbamazepine, vigabatrin, and gabapentin) (117). Unlike most anticonvulsants, topiramate, felbamate, and zonisamide can cause weight loss. 

Tsanaclis et al. [33] described a reversed-phase HPLC method for determination of vigabatrin in plasma after derivatization with phthalal-dehyde. Serum was mixed with y-amino-y-phenylbutyric acid and methanol. Derivatization was carried out with phthaldehyde in borate buffer (pH 9.5) containing 2-mercaptoethanol. The resulting mixture was separated on a column (15 cm x 4.6 mm) of C18 Microsorb (5 /an) with 10 M H3P04-acetonitrile-methanol (6 3 1) as mobile phase with a flow rate of 2 ml/min and fluorimetric detection between 418 and 700 nm (excitation at 370 nm). The detection limit was 0.08 fig/ml of vigabatrin. The CVs were 9%, 5%, and 5% at 2.14, 20.1, and 83.61 fig/ml/min, respectively. Common anticonvulsant did not interfere. 

Drug therapy includes the use of anticonvulsant or anti-epileptic drugs, such as sodium valproate, sodium phenytoin, lamotrigine, vigabatrin. 

Should certain antiepileptic drugs be contraindicated in patients with active psychosis Unfortunately there is not enough solid information to answer this question. Undoubtedly, anticonvulsants that are less likely to cause psychosis (lamotrigine, carbamazepine, oxcarbaze-pine, valproate) should be preferred (52,53). However, patients with psychoses have been successfully treated even with drugs that are believed to be associated with psychosis, such as vigabatrin. For example, in a prospective study in 10 patients with psychosis and epilepsy to whom vigabatrin was added, there was no aggravation of the psychiatric disorder (54). 

Vigabatrin is an effective anticonvulsant medication that selectively increases brain and retinal y-aminobutyric acid. 

Bromide (1857) was the first drug to be used for the treatment of epilepsy, but it is now obsolete. Phenobarbital, introduced in 1912, controlled patients resistant to bromides. The next success was the discovery in 1938 of phenytoin (a hydantoin) which is structurally related to the barbiturates. Since then many other drugs have been discovered, but phenytoin still remains a drug of choice in the treatment of major epilepsy. Over the past ten years there has been a dramatic increase in the number of new anticonvulsant drugs (vigabatrin, gabapentin, lamotrigine, topiramate, oxcarbazepine, levetiracetam), but none has been shown to be superior to the major standard anticonvulsants (phenytoin, carbamazepine and sodium valproate). 

Vigabatrin is effective in partial, secondary generalised seizures which are not satisfactorily controlled by other anticonvulsants, and in infantile spasms, as monotherapy. It worsens absence and myoclonic seizures... 

Of the newer anticonvulsants, lamotrigine, gabapentin, tiagabine, and vigabatrin have little or no teratogenic potential in animals, whereas oxcarbazepine and topira-mate are teratogenic in rodents. However, animal studies are not necessarily apphcable to humans and chnical data are stiU insufficient to assess the effects of newer drugs on the development of the human fetus (153). 

A review of the second-generation anticonvulsants reveals that screening or serendipity led to the development of felbamate (10), 1am-otrigine (11), zonisamide (13), topiramate (15), and levetiracetam (16) on the other hand, clobazam (4d) and oxcarbazepine (12) were developed by structural variation of known agents (78). Only three, vigabatrin (8), gabapentin (9), and tiagabine (14), were developed by mechanism-based rational development (78). 

Designed to inhibit GABA-transaminase, vigabatrin is an anticonvulsant that can be effective in patients resistant to other drugs. 

FIGURE 104 Vigabatrin inhibits GABA transaminases and has anticonvulsant properties. 

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