How do barbiturates, including phenobarbital and pentobarbital, primarily enhance inhibition?

Label:chem

Topic
Barbiturates are known for their GABA-ergic properties and their interaction with neurotransmitter receptors.
Answer
Phenobarbital enhances inhibition by interacting with the GABA$_{A}$-Receptor. Barbiturates potentiate GABA-induced chloride currents by prolonging periods during which bursts of channel opening occur, unlike benzodiazepines, which increase the frequency of these bursts. Additionally, phenobarbital and pentobarbital can inhibit high-voltage activated calcium currents at therapeutic serum concentrations. Sub-anesthetic concentrations of barbiturates can also reduce glutamate-induced depolarizations via AMPA subtypes of glutamate receptors.
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