GABAA Receptor Complex and Sedative-Hypnotic Drugs
Many CNS depressants, including alcohols, barbiturates, benzodiazepines, and carbamates, produce sedation (reduction of anxiety) or hypnosis (induction of sleep). Sedativehypnotics show considerable chemical diversity but share an ability to modulate Cl− influx via interaction with the GABAA receptor–Cl− channel complex, a heteroligomeric glycoprotein comprising 5 or more membranespanning subunits. Various subunit combinations give rise to multiple receptor subtypes. GABA enhances Cl− influx by binding to α or β subunits. Cl− influx hyperpolarizes the neuron and makes it less likely to fire in response to stimulation (EPSPs). Barbiturates depress neuronal activity by facilitating and prolonging inhibitory effects of GABA and Gly by interacting with Cl− channel sites and increasing the duration of GABAmediated channel opening. Benzodiazepines (see Figure 39) bind to specific receptor sites on the complex and increase the frequency of GABAmediated channel opening.