Gabapentin: In Epilepsy and Neuropathic Pain

Abstract

Gabapentin is a new anticonvulsant and is also effective for neuropathic pain. The chemical structure of gabapentin is a GABA molecule covalently bound to a lipophilic cyclohexane ring. However, gabapentin does not bind to any subtypes of GABA receptor or GABA transporter. Several hypotheses of cellular mechanisms of gabapentin are proposed. Gabapentin increases GABA and decreases glutamate level in the brain by affecting various cytosolic enzyme such as enhancement of glutamic acid decarboxylase (GAD) and inhibition of branched-chain amino acid aminotransferase. Gabapentin also binds with high affinity to a novel binding site in the brain. This binding site is believed to be an auxiliary subunit of voltage-sensitive Ca⁺⁺ channels. The role of this subunit in epilepsy and neuropathic pain remains to be verified. Gabapentin has favorable pharmacokinetic profile. Its absorption depends on the transport via L-system amino acid. The drug is not metabolized and excreted unchanged in urine. It is not an enzyme inducer or inhibitor and has a broad therapeutic index. Several randomized controlled trial have demonstrated the efficacy of gabapentin both in epilepsy and neuropathic pain. Common side effects of gabapentin are CNS side effects such as somnolence, dizziness, nystagmus and weight gain.