GABA seizures

The anticonvulsant progabide 24) is useful in a wide variety of seizure disorders. It was synthesiied as a y-aniinobutync acid (GABA) prodrug but its activity appears to reside in the parent drug and its acid metabolite, as well as the GABA liberated [21],... 

Severe withdrawal symptoms, including insomnia, irritability, agitation, withdrawal seizures, and delirium, have been described in both mice and humans chronically exposed to the anesthetics nitrous oxide, ether, and isoflurane (Arnold et al. 1993 Delteil et al. 1974 Deniker et al. 1972 Harper et al. 1980 Smith et al. 1979 Tobias 2000). These symptoms were controlled with the administration of y-aminobutyric acid (GABA)-ergic agents such as pentobarbital, midazolam, and diazepam (Arnold et al. 1993 Hughes et al. 1993). 

These have yielded few data apart from reports of reduced GABA and taurine in the CSF of baboons with spontaneous seizures. 

Introduced initially for absence seizures, this drug is now known to be effective in and used to treat tonic lonic seizures and most types of epilepsy. It was found to inhibit GABA transaminase and so elevate GABA concentrations and inhibition. This is achieved, however, over a slower time-course than its anti-seizure effect, especially experimentally, which is now thought to be due to its phenytoin-like, use-dependent block of sodium channels. Since, unlike phenytoin, the full effect of valproate takes some weeks to develop, its slower effect on GABA metabolism and activity should not be ignored. 

The major inhibitory neurotransmitter in the cerebral cortex is y-aminobutyric acid (GABA). It attaches to neuronal membranes and opens chloride channels. When chloride flows into the neuron, it becomes hyperpolarized and less excitable. This mechanism is probably critical for shutting off seizure activity by controlling the excessive neuronal firing. Some antiepileptic drugs, primarily barbiturates and benzodiazepines, work by enhancing the action of GABA. 

Disorders of GABA Vitamin B6-dependent seizures Often an absence of succinic semialdehyde dehydrogenase Hypotonia, ataxia, mental retardation in older child. Increased urine 4-OH-butyric acid. Pyridoxine (B6-dependent disorder) Inhibitors of GABA transaminase... 

Gabapentin inhibits high-voltage activated Ca channels and elevates human brain GABA levels. It is a second-line agent for patients with partial seizures who have failed initial treatment. It may also have a role in patients with less severe seizure disorders, such as new-onset partial epilepsy, especially in elderly patients. 

Gonsalves, S. F Twitchell, B Harbaugh, R. E., Krogsgaard-Larsen, P., and Schousboe, A. (1989) Anticonvulsant activity of the glial GABA uptake inhibitor, THAO, in chemical seizures. Eur. J. Pharmacol. 168,265-268. 

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