Pregabalin, a new analog of the neurotransmitter gamma-aminobutyric acid (GABA), is a ligand for the α-2-δ subunit of voltage gated calcium channels with anticonvulsant, analgesic, and anxiolytic properties. Pregabalin binds potently to the α2-δ subunit resulting in modulation of calcium channels and reduction in the release of several neurotransmitters, including glutamate, norepinephrine, serotonin, dopamine, and substance P. It has predictable absorption across the gastrointestinal tract, is neither metabolized nor protein-bound, and has minimal drug-drug interactions. It is effective with two or three-times daily dosing in a dose range of 150 to 600 mg daily. Several published prospective, randomized clinical trials in postherpetic neuralgia (PHN) and painful diabetic peripheral neuropathy (DPN) demonstrate pain relief, decreased sleep interference, and improvements in several secondary outcome measures. The 50% responder rates for PHN and DPN compare favorably with other first-line agents for neuropathic pain. Pregabalin is well tolerated in most patients with infrequent severe adverse effects. Pregabalin is an important addition to the treatment armamentarium for neuropathic pain. Pregabalin has demonstrated efficacy as an adjunctive treatment for epilepsy and in several neuropathic pain models, Fibromyalgia, generalized anxiety disorder (GAD) and social anxiety disorder. Data supporting clinical efficacy in such a wide range of clinical conditions is unique, particularly in a new medication. These findings have led some to refer to pregabalin as a "neuromodulator" rather than simply an anticonvulsant with pain-relieving properties. This review discusses the pharmacology of this medication as well as clinical application based on recent clinical trials.

KeywordsPregabalin, α-2-δ subunit, Neuropathic pain