Gabapentin is a medicine that may be used for the treatment of certain seizure disorders or nerve pain.
Gabapentin is a structural analogue of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) that was first approved for use in the United States in 1993.
It was originally developed as a novel anti-epileptic for the treatment of certain types of seizures – today it is also widely used to treat neuropathic pain.
Gabapentin has some stark advantages as compared with other anti-epileptics, such as a relatively benign adverse effect profile, wide therapeutic index, and lack of appreciable metabolism making it unlikely to participate in pharmacokinetic drug interactions.
It is structurally and functionally related to another GABA derivative, pregabalin.
Experts aren’t sure exactly how gabapentin works, but research has shown that gabapentin binds strongly to a specific site (called the alpha2-delta site) on voltage-gated calcium channels. This action is thought to be the mechanism for its nerve-pain relieving and anti-seizure properties.
Gabapentin enacarbil (brand name Horizant) is a prodrug of gabapentin which has been designed to overcome the limitations of gabapentin, such as poor absorption and a short duration of action. Gabapentin enacarbil is effective for restless legs syndrome (RLS) and postherpetic neuralgia (nerve pain that occurs following Shingles).
Gabapentin belongs to the group of medicines known as anticonvulsants.
The precise mechanism through which gabapentin exerts its therapeutic effects is unclear.
The primary mode of action appears to be at the auxillary α2δ-1 subunit of voltage-gated calcium channels (though a low affinity for the α2δ-2 subunit has also been reported).
The major function of these subunits is to facilitate the movement of pore-forming α1 subunits of calcium channels from the endoplasmic reticulum to the cell membrane of pre-synaptic neurons.
There is evidence that chronic pain states can cause an increase in the expression of α2δ subunits and that these changes correlate with hyperalgesia.
Gabapentin appears to inhibit the action of α2δ-1 subunits, thus decreasing the density of pre-synaptic voltage-gated calcium channels and subsequent release of excitatory neurotransmitters.
It is likely that this inhibition is also responsible for the anti-epileptic action of gabapentin.
There is some evidence that gabapentin also acts on adenosine receptors and voltage-gated potassium channels, though the clinical relevance of its action at these sites is unclear.