Hanyang Med Rev.  2011 May;31(2):55-62. 10.7599/hmr.2011.31.2.55.

Clinical Application of alpha2-delta Ligand

• Shim JH

• KMID: 2168180
• DOI: http://doi.org/10.7599/hmr.2011.31.2.55

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.

Keyword

Alpha2-delta ligand; Calcium channel; Chronic pain; Neuropathic pain

MeSH Terms

Amines
Animals
Calcium Channels
Central Nervous System Sensitization
Chronic Pain
Cyclohexanecarboxylic Acids
gamma-Aminobutyric Acid
Horns
Ligands
Neuralgia
Neurotransmitter Agents
Nociceptors
Pain Management
Spinal Cord
Pregabalin
Amines
Calcium Channels
Cyclohexanecarboxylic Acids
Ligands
Neurotransmitter Agents
gamma-Aminobutyric Acid

Figure

• 

  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.

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