Jae Hang Shim

doi:10.7599/hmr.2011.31.2.55

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Shim: Clinical Application of α2-δ Ligand

Review Article

Hanyang Medical Reviews

Hanyang Medical Reviews 2011; 31(2): 55-62.

Published online: 31 May 2011

DOI: https://doi.org/10.7599/hmr.2011.31.2.55

Clinical Application of α₂-δ Ligand

Jae Hang Shim, M.D., Ph.D.

Department of Anesthesiology and Pain Medicine, College of Medicine, Hanyang University, Seoul, Korea.

Corresponding author (jhshim@hanyang.ac.kr)

Received 8 April 2011 Accepted 6 May 2011

Abstract

Chronic pathological pain is sustained by mechanisms of peripheral and central sensitization, which are being increasingly investigated at the molecular and cellular levels. The molecular mechanisms of sensitization that occur in peripheral nociceptors and the dorsal horns of the spinal cord are putative targets for context-dependent drugs. Pregabalin and gabapentin are analogs of the neurotransmitter gamma-aminobutyric acid (GABA). They are alpha2-delta ligands that have analgesic, anticonvulsant, and anxiolytic activity. Alpha2-delta is an auxiliary protein associated with voltage-gated calcium channels. They bind potently to the subunit resulting in modulation of calcium channels and reduction in the release of several neurotransmitters. This review discusses the pharmacology of these medications briefly as well as available clinical applications in pain management.

Keywords: Alpha2-delta ligand, Calcium channel, Chronic pain, Neuropathic pain

Figures and Tables

Fig. 1

The mechanism of action of pregabalin. Pregabalin modulates hyperexcited neurons via the following mechanism: Pregabalin binds to presynaptic neurons at the alpha2-delta (α 2-δ) subunit of voltage-gated calcium channels. Drug binding reduces calcium influx into presynaptic terminals. Decreased calcium influx reduces excessive release of excitatory neurotransmitters (eg, glutamate, substance P, noradrenaline). Data on file, Pfizer Inc, New York, NY, USA.

Fig. 2

Chemical structure of GABA, gabapentin and pregabalin Gabapentin and pregabalin are structural analog of GABA, but not GABA mimetic.

Table 1

Pharmacokinetic Profiles of Pregabalin and Gabapentin

Modified from Chiechio S, et al. Pregabalin in the treatment of chronic pain: an overview. Clin Drug Investig 2009;29:203-13

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