Ca2+ channel α2δ ligands: novel modulators of neurotransmission

The term ‘Ca2+ channel α2δ ligands’ has recently been applied to an evolving drug class that includes gabapentin (Neurontin®) and pregabalin (Lyrica®), and reflects significant progress over the past decade in elucidating the mechanism of action of these drugs: a novel, specific action at one of the subunits constituting voltage-sensitive Ca2+ channels. Binding of these ligands to the α2δ subunit is considered to explain their usefulness in treating several clinical disorders, including epilepsy, pain from diabetic neuropathy, postherpetic neuralgia and fibromyalgia, and generalized anxiety disorder. The evidence indicates a relationship between α2δ subunit binding and the modulation of processes that subserve neurotransmission. This modulation is characterized by a reduction of the excessive neurotransmitter release that is observed in certain neurological and psychiatric disorders.