[9][10] Gabapentinoids are approved for the treatment of epilepsy, postherpetic neuralgia, neuropathic pain associated with diabetic neuropathy, fibromyalgia, generalized anxiety disorder, and restless legs syndrome.

[13] The main side-effects include: a feeling of sleepiness and tiredness, decreased blood pressure, nausea, vomiting and also glaucomatous visual hallucinations.

[14] Gabapentinoids are high affinity ligands of the α2δ protein that was first described as an auxiliary subunit of certain voltage-gated calcium channels (VGCC).

[1] In most cases, gabapentinoid drugs do not seem to directly alter the action of VGCC and instead reduce the release of certain excitatory neurotransmitters.

[17] Gabapentinoids alter the function of these additional α2δ binding proteins, and these have been proposed as mediators of drug actions.

Pregabalin has demonstrated significantly greater potency (about 2.5-fold) than gabapentin in clinical studies[21] and mirogabalin is even more potent in vivo.

[1] The LAT1 is easily saturable, so the pharmacokinetics of gabapentin are dose-dependent, with diminished bioavailability and delayed peak levels at higher doses.

[24][25] Conversely, the oral bioavailability of pregabalin is greater than or equal to 90% across and beyond its entire clinical dose range (75 to 900 mg/day).

[29] Because of its short elimination half-life, gabapentin must be administered 3 to 4 times per day to maintain therapeutic levels.

[3][4] Specifically, pregabalin is (S)-(+)-3-isobutyl-GABA, phenibut is 3-phenyl-GABA,[28] and gabapentin is a derivative of GABA with a cyclohexane ring at the 3 position (or, somewhat inappropriately named, 3-cyclohexyl-GABA).

[38][39][40] Recently, a detailed three dimensional molecular structure of the α2δ-1 protein with gabapentin and alternatively with L-leucine bound at the gabapentinoid binding site has been published PDB: 8FD7​.

The gabapentinoids also closely resemble the α-amino acids L-leucine and L-isoleucine, and this may be of greater relevance in relation to their pharmacodynamics than their structural similarity to GABA.

[46] An extended-release formulation of gabapentin for once-daily administration, under the brand name Gralise, was approved in the United States for the treatment postherpetic neuralgia in January 2011.

[47][48] Pregabalin, under the brand name Lyrica, was approved in Europe in 2004 and was introduced in the United States in September 2005 for the treatment of epilepsy, postherpetic neuralgia, and neuropathic pain associated with diabetic neuropathy.

[54] Phenibut, marketed under the brand names Anvifen, Fenibut, and Noofen, was introduced in Russia in the 1960s for the treatment of anxiety, insomnia, and a variety of other conditions.

[9] Baclofen marketed under the brandname of Lioresal was introduced in the United States in 1977 for the treatment of spasticity is chemically similar to phenibut but is usually not considered a gabapentinoid.

Mirogabalin, under the brand name Tarlige, was approved for the treatment of neuropathic pain and postherpetic neuralgia in Japan in January 2019.

[56] A longitudinal trend study analyzed multinational sales data, revealing an overall increase in gabapentinoid consumption across 65 countries and regions from 2008 to 2018.

This comprehensive analysis underscores the widespread use of gabapentinoids beyond their initial antiseizure applications, reflecting their role in treating a broad spectrum of conditions.