Gabapentin enhances slow-wave sleep in patients with primary insomnia. It also improves sleep quality by elevating sleep efficiency and decreasing spontaneous arousal. The results suggest that gabapentin may be beneficial in the treatment of primary insomnia. Drug dependence
Gabapentin is moderately effective in reducing the symptoms of alcohol withdrawal and associated craving. The evidence in favor of gabapentin is weak in the treatment of alcoholism: it does not contribute to the achievement of abstinence, and the data on the relapse of heavy drinking and percent of days abstinent do not robustly favor gabapentin; it only decreases the percent days of heavy drinking.Gabapentin is ineffective in cocaine dependence and methamphetamine use, and it does not increase the rate of smoking cessation. Gabapentin does not significantly reduce the symptoms of opiate withdrawal. There is insufficient evidence for its use in cannabis dependence. Other
Gabapentin is recommended as a first-line treatment of the acquired pendular nystagmus, torsional nystagmus, and infantile nystagmus; however, it does not work in periodic alternating nystagmus.Gabapentin decreases the frequency of hot flashes in both menopausal women and patients with breast cancer. However, antidepressants have similar efficacy, and treatment with estrogen more effectively prevents hot flashes.Gabapentin reduces spasticity in multiple sclerosis and is prescribed as one of the first-line options. It is an established treatment of restless legs syndrome. Gabapentin alleviates itching in kidney failure (uremic pruritus) and itching of other causes. It may be an option in essential or orthostatic tremor.
Pharmacology
Pharmacodynamics
Gabapentin is a ligand of the α2δ calcium channel subunit. α2δ is an auxiliary protein connected to the main α1 subunit (the channel-forming protein) of high voltage activated voltage-dependent calcium channels (L-type, N-type, P/Q type, and R-type). Gabapentin is not a direct channel blocker: it exerts its actions by disrupting the regulatory function of α2δ and its interactions with other proteins. Gabapentin prevents delivery of the calcium channels to the cell membrane, reduces the activation of the channels by the α2δ subunit, decreases signaling leading to neurotransmitters release, and disrupts interactions of α2δ with NMDA receptors, neurexins, and thrombospondins. Out of the four known isoforms of α2δ protein, gabapentin binds with similar high affinity to two: α2δ-1 and α2δ-2. Most of the pharmacological properties of gabapentin are explained by its binding to just one isoform – α2δ-1.The endogenous α-amino acids L-leucine and L-isoleucine, which resemble gabapentin in chemical structure, bind α2δ with similar affinity to gabapentin and are present in human cerebrospinal fluid at micromolar concentrations. They may be the endogenous ligands of the α2δ subunit, and they competitively antagonize the effects of gabapentin. Accordingly, while gabapentin has nanomolar affinity for the α2δ subunit, its potency in vivo is in the low micromolar range, and competition for binding by endogenous L-amino acids is likely to be responsible for this discrepancy.Gabapentin is a potent activator of voltage-gated potassium channels KCNQ3 and KCNQ5, even at low nanomolar concentrations.