Does valproate inhibit GABA transaminase?
A preferential effect of valproate on gamma-aminobutyric acid (GABA) in the nerve terminal compartment has been proposed. Gamma-vinyl GABA, an irreversible inhibitor of GABA-transaminase (GABA-T) causes a preferential increase in the GABA compartment of the non-nerve terminal.
How does valproic acid affect GABA?
Valproic acid may also block the reuptake of GABA, thereby increasing GABA levels in the brain. High GABA levels can help decrease the uncontrolled firing of neurons that cause seizures in Batten disease patients. Valproic acid can also act as an ion channel modulator.
How does sodium valproate increase GABA?
Although valproate does not directly interact with postsynaptic GABA receptors, it does increase regional neuronal concentrations of GABA by both inhibiting its metabolism and increasing its synthesis.
What is the mechanism of action of valproate?
Pharmacodynamics. Although the mechanism of action of valproate is not fully understood, traditionally, its anticonvulsant effect has been attributed to the blockade of voltage-gated sodium channels and increased brain levels of gamma-aminobutyric acid (GABA).
What inhibits GABA transaminase?
Inhibition of GABA transaminase enzymes reduces the degradation of GABA, leading to increased neuronal GABA concentrations. Examples include valproic acid, vigabatrin, phenylethylidenehydrazine (and drugs that metabolize to it, such as phenelzine), ethanolamine-O-sulfate (EOS), and L-cycloserine.
What do GABA reuptake inhibitor do?
Gamma-Aminobutyric acid (GABA) reuptake inhibitors are analogs of gamma-Aminobutyric acid that bind to gamma-aminobutyric acid transporters and inhibit GABA reuptake. This increases extracellular levels of GABA and enhances GABA mediated synaptic activity in the brain.
What neurotransmitter does valproate affect?
Abstract. Sodium valproate is an anticonvulsant which elevates GABA levels in the brain. GABA interacts with dopamine functionally in certain areas of the brain involved in motor behavior such as the nucleus accumbens and the substantia nigra.
What receptors does valproate use?
Valproate has been suggested to mediate the neuronal excitation of N-methyl-D-aspartate (NMDA) glutamate receptors, which is also likely to contribute to its anticonvulsant effect.
How is valproic acid excreted?
Valproic acid concentration in saliva is less than and unrelated to the free drug concentration in plasma. The drug is excreted into breast milk and evidence suggests that it also crosses the placenta.
What does valproic acid inhibit?
Valproic acid inhibits the activity of CYP2C9 at clinically relevant concentrations in human liver microsomes. Inhibition of CYP2C9 can explain some of the effects of valproic acid on the pharmacokinetics of other drugs, such as phenytoin.
What do GABA reuptake inhibitors do?
A GABA reuptake inhibitor (GRI) is a type of drug which acts as a reuptake inhibitor for the neurotransmitter gamma-Aminobutyric acid (GABA) by blocking the action of the gamma-Aminobutyric acid transporters (GATs).
Where is GABA transaminase found?
the CNS
GABA Metabolism. The only GABA metabolizing enzyme is GABA-aminotransferase (GABA-transaminase, GABA-T), which is expressed in all cells of the CNS as well as peripherally. It catalyzes the conversion of GABA to succinic semialdehyde (SSA) concomitantly with conversion of α-ketoglutarate to glutamate (Figure 3(a),(b).