In the central nervous system (CNS), gamma-aminobutyric acid (GABA) is the main main inhibitory neurotransmitter that functions to regulate neuronal firing. GABA exerts its effects through two different kinds of receptors: ionotropic receptors (GABAA R and GABAC R), which produce fast inhibitory signals, and metabotropic receptors (GABAB R), which produce slow inhibitory signals. The GABAB R receptor is a heterodimer that consists of two multi-pass membrane proteins, designated GABAB R1 and GABAB R2, both of which belong to the G protein-coupled receptor family and are highly expressed in brain tissue. Together, GABAB R1 and GABAB R2 play a crucial role in the fine-tuning of inhibitory synaptic transmissions and are implicated in slow wave sleep, muscle relaxation, hippocampal long-term potentiation and antinociception events. Both GABAB R1 and GABAB R2 are regulated by G proteins that have a variety of functions, including activation of potassium channels, inhibition of adenylyl cyclase (A cyclase) activity and modulation of inositol phospholipid hydrolysis.