By Marcello Cherchi, MD PhD
For patients
Gabapentin is a pill that was originally developed for treating seizures, but is sometimes also used for other diseases. Gabapentin can make you sleepy, especially if you take it at the same time as other medications that cause sleepiness.
For clinicians
Overview
Gabapentin is FDA approved for treatment of certain types of seizures and for post-herpetic neuralgia, and it is used off-label in the management of several other conditions. It probably has several mechanisms of action, the main one of which is that it binds to and inhibits voltage-gated calcium channels containing the a2d‑1 subunit, with downstream effects of inhibiting the release of other neurotransmitters. Its main adverse effects include sedation, so care should be taken when used in conjunction with other potentially sedating medications. Gabapentin has been used in the management of several otoneurological conditions.
Introduction
Gabapentin was originally designed as an anti-epileptic medication, but eventually also received FDA approval for post-herpetic neuralgia, and is used off-label in the management of neuropathic pain, fibromyalgia, alcoholism and migraine.
Pharmacology
The structure of the gabapentin molecule resembles that of the inhibitory neurotransmitter GABA (gamma-aminobutyric acid) (Bockbrader et al. 2010; Sills 2006), so one would expect that its pharmacologic mechanism of action would be similar. However, animal and human studies show that the GABA‑like effect of gabapentin is modest; it “does not bind to GABA receptors, is not converted metabolically into GABA, and is neither a substrate for, nor a direct inhibitor of, GABA transport” (Sills 2006). Its predominant effect instead is selective inhibition of voltage-gated calcium channels containing the a2d‑1 subunit (Bockbrader et al. 2010; Sills 2006). Although it has some influence on systems involving the excitatory neurotransmitters glutamate and NMDA, these effects are small, so it remains unclear whether these mechanisms play a significant role in the inhibitory effects of gabapentin (Sills 2006).
Adverse effects
The main adverse effects of gabapentin include sedation.
Cautions and contraindications
Because of the potentially sedating effects of gabapentin, care should be taken when it is used in conjunction with other potentially sedating medications.
Relevance in otoneurology
Gabapentin has been used in the management of several otoneurological disorders, including superior oblique myokymia, congenital nystagmus, visual snow syndrome, opsoclonus, Chiari malformations, oculopalatal tremor, vestibular/vestibulocochlear paroxysmia and migraine associated vertigo.
References
Bockbrader, H. N., D. Wesche, R. Miller, S. Chapel, N. Janiczek and P. Burger (2010). “A comparison of the pharmacokinetics and pharmacodynamics of pregabalin and gabapentin.” Clin Pharmacokinet 49(10): 661-669.
Sills, G. J. (2006). “The mechanisms of action of gabapentin and pregabalin.” Curr Opin Pharmacol 6(1): 108-113.
