Psychopharmacology of Gabapentinoids – Pregabalin and Gabapentin

Posted on:September 27, 2023
Last Updated: February 11, 2024
Time to read: 15–18 minutes

Gabapentinoids (gabapentin and pregabalin) are agents derived from the inhibitory neurotransmitter gamma-aminobutyric acid (GABA), and exert their effects through the alpha2-delta (α2δ) receptors, primarily at intracellular sites requiring active uptake.

Gabapentinoids resemble the amino acid leucine in their mechanism of action and are dependent on facilitated transport across cell membranes through l-amino acid transporters (LAT), resemble leucine in their mechanism of action. [Chincholkar, 2018]

Despite the structural similarity to GABA, gabapentin and pregabalin, initially marketed off-label for pain, do not bind to GABA receptors but have a high affinity for α2δ-1 subunit of voltage-gated calcium channels (VGCCs). They were later FDA-approved for postherpetic neuralgia.