Vigabatrin Tiagabine

Barbiturates phenobarbital 1 Benzodiazepines alprazolam, diazepam, i lorazepam, oxazepam Carbamazepine, ethosuximide, valproic acid, phenytoin, diazepam, lorazepam, gabapentin, lamotrigine, felbamate, topiramate, tiagabin, vigabatrin... 

Vigabatrin (not marketed in United States), tiagabine, topiramate, gabapentin, carbamazepine, lamotrigine... 

Vigabatrin (irreversible GABA aminotransferase inhibitor), zonisamide, lamotrigine (217) (glutamate inhibitor), oxcarbazepine (218), levetiracetam (219), piracetam, tiagabine (220),... 

They are different from vigabatrin (4) in that they are not inhibitors of GABA transaminase, and, in contrast to tiagabine (5), these molecules do not directly inhibit GABA reuptake (Bryans and Wustrow, 1999 Taylor, 1994). 

II.e. 5.2. Interactions between first and second generation AEDs. Felbamate raises plasma concentrations of phenytoin, valproic acid and carbamazepine. Clearance of tiagabine, topiramate and zon-isamide is increased in the presence of an enzyme inducer. Vigabatrin reduces phenytoin concentrations after 4-5 weeks of comedication (via an unknown mechanism). For tiagabine, the elimination half-life may be reduced by 2-3 hours in the presence of an enzyme-induction AED. Lamotrigine elimination is slower if given with valproic acid. Topiramate reduces elimination of phenytoin. 

Tiagabine blocks neuronal uptake of GABA and has reported benefits in panic disorder and PTSD (Lydiard 2003). Topiramate has complex actions on GABA and glutamate and was found to be helpful for some symptoms of PTSD (Berlant and van Kammen 2002). Vigabatrin inhibits GABA metabolism and has been shown to block induced panic attacks in healthy volunteers (Zwanzger et al. 2001). 

Neither vigabatrin nor gabapentin caused porphyrin accumulation in chicken embryo cultured liver cells, whereas felbamate, lamotrigine, and tiagabine were por-phyrinogenic in this model (129). For gabapentin, safety in porphyrias has been confirmed in preliminary clinical observations (SEDA-19, 70) (SEDA-20, 62). 

Angehagen M, Ben-Menachem E, Ronnback L, Hans-son E. Novel mechanisms of action of three antiepileptic drugs, vigabatrin, tiagabine, and topiramate. Neurochem Res. 2003 28 333-340. 

Visual field defects associated with various antiepUeptic drugs (carbamazepine, diazepam, gabapentin, pheny-toin, tiagabine, and vigabatrin) have been reviewed (19). The true frequency is unknown, but in a retrospective study in 158 patients with partial epilepsy visual field defects were detected in 21 (13%) 13 patients had concentric visual field constriction without subjective spontaneous manifestations. Of these 13 patients, 9 were taking vigabatrin. 

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). 

Sills GJ, Patsalos PN, Butler E, Forrest G, Ratnaraj N, Brodie MJ. Visual field constriction accumulation of vigabatrin but not tiagabine in the retina. Neurology 2001 57(2) 196-200. 

Vigabatrin acts by blocking GABA-T, the enzyme responsible for the breakdown of GABA (Fig. 6.5) tiagabine acts by inhibiting the reuptake of the neurotransmitter. 

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). 

Newer agents Felbamate, gabapentin, lamotrigine, tiagabine, topiramate, vigabatrin ... 

Fraser CM, Siiis GJ, Butier E, et ai. Effects of vaiproate, vigabatrin, and tiagabine on GABA uptake into human astrocytes cuitured from fetai and aduit brain tissue. Epiieptic Disord 1999 1 153-157. 

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