Update on signaling mechanisms of the GABA_B receptors

Abstract

GABA_B receptors (GABA_BR) are dimerized receptors composed of GABA_B1 and GABA_B2 subunits. There are many functional proteins that bind to GABA_BR, and they are among the candidate targets in developments for drug discovery. Baclofen, a central muscle relaxant, acts on GABA_BR in the spinal cord and reduces spasticity. However, the blood-brain barrier is largely impermeable to baclofen, so intrathecal baclofen therapy (ITB) has been developed to increase the baclofen concentration in the spinal cord. Baclofen resistance, the state in which baclofen does not act very well, may develop during ITB therapy, and it is thought to be due to desensitization of GABA_BR. It is thus important to support patients who develop baclofen resistance, and research on the prevention of baclofen resistance, through elucidation of its mechanisms, is an important issue