Category: receptor_pharmacology
Major inhibitory neurotransmitter system. GABA binding to pentameric GABA-A chloride channels (α/β/γ subunit composition) increases Cl⁻ conductance, hyperpolarizes the neuron, and dampens excitability. Distinct allosteric sites accept benzodiazepines (α1/2/3/5 + γ2 interface — positive allosteric modulators that enhance GABA's effect but require GABA to act), barbiturates (β subunit — at higher doses become direct channel openers without GABA, hence the larger toxicity tail), Z-drugs (α1-selective benzodiazepine-site binders, biased toward sedation over anxiolysis), neurosteroids (allopregnanolone — δ subunit-containing extra-synaptic receptors), and propofol / etomidate (β3 subunit — direct openers like barbiturates). Alcohol's CNS-depressant action is partly GABA-A potentiation at α4/δ extra-synaptic receptors. The GABA-A vs GABA-B split matters — baclofen is a metabotropic GABA-B agonist (Gi-coupled), not a GABA-A modulator, despite both being "GABA-ergic".