Possible Interaction: Anticonvulsants and Gamma-Aminobutyric Acid

“Recent in vivo MRS studies suggest that cerebral ggr;-aminobutyric acid (GABA) increases occur with the administration of certain anticonvulsants in humans.”

“Gamma-vinyl GABA (GVG) is a new anticonvulsant drug that enhances levels of GABA in the brain by irreversibly inhibiting GABA transaminase.”

“In addition, increased GABA levels are also known to elicit an anticonvulsant effect in patients with epilepsy.”

“Abstract Anxiolytics and anticonvulsants generally positively modulate the action of GABA , whereas many convulsants (including the chloride channel blocker picrotoxinin) negatively modulate the action of GABA on GABAA receptors.”

“The fast inhibitory actions of GABA are mediated by GABA type A receptors (GABA(A)Rs); they mediate both phasic and tonic inhibition in the brain and are the principle sites of action for anticonvulsant , anxiolytic, and sedative-hypnotic agents that include benzodiazepines, barbiturates, neurosteroids, and some general anesthetics.”

“We previously found that the endogenous anticonvulsant adenosine , acting through A2A and A3 adenosine receptors (ARs), alters the stability of currents ( IGABA ) generated by GABAA receptors expressed in the epileptic human mesial temporal lobe (MTLE).”

“This transporter-mediated GABA release is enhanced by the anticonvulsants gabapentin and vigabatrin.”

“The hypothesis … the anticonvulsant actions of these drugs may be due to their ability to enhance the actions of GABA at CNS synapses is an attractive one, but many questions remain: Do all CNS benzodiazepine receptors interact with GABA sites, and are all GABA receptors linked to benzodiazepine sites?”

“ Convulsant agents such as picrotoxin and bicuculline appear to act by impairing the functioning of GABA at the postsynaptic receptor site, but virtually nothing is known about the attendant molecular events although a major expansion of knowledge in this area may be expected within the next decade.”

“This depolarizing action of GABA likely contributes to the lowered seizure threshold, increased seizure propensity, and poor efficacy of GABAergic anticonvulsants among infants.”