Pregabalin (PGB) is used for the treatment of epilepsy and neuropathic pain; however, even though PGB is known to bind to high-affinity α2-δ auxiliary subunits in voltage-gated calcium channels, its mechanism of action is not fully understood. Di Guilmi et al. studied the acute mechanism of PGB on excitatory neurotransmitter release at principal neurons of mouse medial nucleus of the trapazoid body (MNTB). PGB modulates glutamatergic neurotransmission at the calyx of Held-MNTB synapse by reducing presynaptic Ca2+ influx through Cav2.1 channels, decreasing the number of inactivated presynaptic Cav2.1 channels, decreasing short-term facilitation of presynaptic Cav2.1 channels, and accelerating the τ-on of calcium channels. These results provide a novel mechanism of action underlying short-term PGB effects on synaptic transmission and clearly demonstrate that PGB acts as a modulator instead of a classic channel blocker of calcium channels. These results also suggest that PGB modulation of activation/inactivation properties of Cav2.1 channels is in accordance with the observed PGB clinical antiepileptic effects. Further characterization of PGB actions on both hippocampal and cortical circuits will be central to understanding its pharmacological action to treat pathologic conditions such as epilepsy and migraine.
See article at J Pharmacol Exp Ther 2011, 336:973–982.
- Copyright © 2011 by The American Society for Pharmacology and Experimental Therapeutics