GABA_B Receptors

GABA_B receptors are widely distributed within the central nervous system, and are found on pre- and post-synaptic membranes, but show low density. The highest concentrations are found in the cerebellum, frontal cortex and specific thalamic nuclei. They are also found on autonomic nerves in the periphery.

On the presynaptic membrane GABA_B receptors inhibit neurotransmitter release, including acting as autoreceptors to regulate the release of GABA. When located on excitatory presynaptic terminals, they regulate glutamate release. These actions occur via the inhibition of Ca²⁺ channels, mediated by the G-protein β/γ subunits, and subsequent decrease in Ca²⁺ influx in response to an arriving action potential. Postsynaptic GABA_B receptors mediate slow, inhibitory synaptic transmission, through the activation of K_IR channels that mediate the late phase of the inhibitory postsynaptic potential.

Baclofen, a GABA derivative and GABA_B agonist, is the only widely clinically available drug targeting the GABA_B receptor. It was originally developed as a treatment of epilepsy, but showed disappointing results. It is now primarily used to treat spastic movement associated with multiple sclerosis and cerebral palsy. Baclofen has also been studied for the treatment of alcohol addiction. Similarly, activation of the GABA_B receptor, with an agonist or a positive allosteric modulator, is thought to reduce the craving for addictive drugs, such as cocaine.

External sources of pharmacological information for GABA_B Receptors :

• IUPHAR Receptor Code

• BJP Guide