Pharmacology of Vigabatrin

Sabers, Anne; Gram, Lennart

doi:10.1111/j.1600-0773.1992.tb00465.x

Cited by 50 publications

(19 citation statements)

References 65 publications

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“…1 Those that have advanced to the clinic include the GABA B receptor agonist baclofen an antispastic agent, 2,3 the GABA transaminase inhibitor vigabatrin, 4,5 and the putative GABA prodrug progabide 6 which are anticonvulsant agents (Fig. 1).…”

Section: R a T I O N A L Ementioning

confidence: 99%

3-Substituted GABA analogs with central nervous system activity: A review

Bryans¹,

Wustrow²

1999

Med. Res. Rev.

281

153

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Section: R a T I O N A L Ementioning

confidence: 99%

3-Substituted GABA analogs with central nervous system activity: A review

Bryans¹,

Wustrow²

1999

Med. Res. Rev.

281

153

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“…Despite these observations, the precise manner in which VGB prevents seizures remains unclear. The AED effect of VGB may relate to the fact that GABA-T inhibition results in a greater releasable pool of GABA, identified in synaptosomes (1 38), more than simply to an elevation in whole-brain GABA levels (139). Thus, larger amounts of GABA may be made available and released into the presynaptic space during epileptic seizures to provide sufficient postsynaptic inhibition of GABA receptors.…”

Section: Vigabatrinmentioning

confidence: 99%

The Pharmacologic Basis of Antiepileptic Drug Action

1999

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Summary:The development of medications used in the treatment of epilepsy has accelerated over the past decade, and has benefited from a parallel growth in our knowledge of the basic mechanisms underlying neuronal excitability and synchronization. This understanding of the pharmacologic basis of antiepileptic drug (AED) action has, in large part, arisen from recent advances in cellular and molecular biology, coupled with avenues of drug discovery that have departed somewhat from the largely empiric approaches of the past. Physicians now have available to them an ever-growing armentarium of AEDs, neTherapy with antiepileptic drugs (AEDs) remains the mainstay of treatment of patients with epilepsy. Before the Victorian era, therapeutic approaches to epilepsy were largely based on superstition and charlatanism. The first demonstrably effective chemotherapy relied on the use of nonspecific depressants of the central nervous system. Sir Charles Locock introduced bromides in the mid-nineteenth century for the treatment of catamenial epilepsies, and phenobarbital (PB) was adopted in 1912 after the observations of Hauptmann (l), who used that compound to sedate a ward of noisy psychiatric patients and those with epilepsy during the night. Introduction of more specific AEDs for clinical application followed the availability of the first animal-seizure model: the maximal electroshock (MES) model (2). The history of AED design has recently been reviewed in some detail (3).The relation of the human epilepsies to the animal models commonly used for AED development, and to the cellular membrane physiology underlying neuronal excitability, continues to be an imperfect one (Fig. 1) cessitating a firmer appreciation of their mechanisms of action if more rational approaches toward both clinical application and research are to be adopted. An important example in this regard is the concept of rational polypharmacy for patients with epilepsy who are refractory to monotherapy. This review summarizes our current understanding of the molecular targets of clinically significant AEDs, comparing and contrasting their differing mechanisms of action. Key Words: Antiepileptic drug-AED-Anticonvulsant-Mechanism-%-zure-Epilepsy-Ion channel.threshold pentylenetetrazol (PTZ) test in mice (see Table 1) have been carefully standardized (4). The MES model has served to identify AEDs that are functionally similar to phenytoin (PHT), and most of these compounds display in common the ability to inactivate voltage-dependent Na+ channels in a use-dependent fashion. Such compounds suppress sustained repetitive firing in cultured neurons. Activity in this model seems highly predictive of the ability of those AEDs to protect against partial and secondarily generalized tonic-clonic seizures (Fig. 2). Carbamazepine (CBZ), as well as several newer agents such as felbamate (FBM), gabapentin (GBP), lamotrigine (LTG), and topiramate (TPM), fit this model of AED activity. Some of these (i.e., PHT, CBZ, LTG) may also attenuate the release of excitatory neurotransmi...

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“…The systemic administration of vigabatrin causes a dose-dependent prolonged elevation of whole-brain GABA levels in humans and rodents [Grove et al, 1981;Jung et al, 1977;Petroff et al, 1996]. Vigabatrin is used clinically for the treatment of partial complex seizures in both pediatric and adult patients [Rey et al, 1992;Sabers and Gram, 1992].…”

Section: Studying Neurotransmitter Interactions With Petmentioning

confidence: 99%

Development of a GABAergic treatment for substance abuse using PET

Gerasimov

Dewey

2003

Drug Development Research

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Development of an effective treatment for substance abuse relies on a better understanding of the nature of the brain reward circuitry and neurotransmitter systems regulating the mechanisms responsible for drug abuse, addiction, and dependence. The use of positron emission tomography (PET) enables the direct assessment of pharmacokinetic and pharmacodynamic events in vivo. We demonstrated that administration of gamma-vinyl gamma aminobutyric acid (GVG, vigabatrin), acting through potentiation of GABAergic tone, leads to decreases in brain extracellular dopamine concentrations as measured with PET and in vivo microdialysis. This knowledge, combined with the notion that addictive drugs share the ability to stimulate dopaminergic neurotransmission, suggests a novel GABAergic strategy for the treatment of substance abuse. Over the past several years PET and in vivo microdialysis, combined with an array of behavioral tests, have demonstrated the potential utility of this approach. Taken together, our data support the use of vigabatrin for the treatment of multiple drug addictions. Drug Dev. Res. 59:240-248, 2003.

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Pharmacology of Vigabatrin

Cited by 50 publications

References 65 publications

3-Substituted GABA analogs with central nervous system activity: A review

3-Substituted GABA analogs with central nervous system activity: A review

The Pharmacologic Basis of Antiepileptic Drug Action

Development of a GABAergic treatment for substance abuse using PET

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