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.
