gabapentinoidid

Gabapentinoids are a class of prescription drugs that includes gabapentin, pregabalin, and mirogabalin. They are used to treat certain types of neuropathic pain and epilepsy, among other indications in some regions. Although they share structural similarity with the neurotransmitter GABA, they do not act on GABA receptors and do not mimic GABA directly.

Mechanism of action

Gabapentinoids bind to the alpha-2-delta subunit of voltage-gated calcium channels in the central nervous system. This binding reduces the release of excitatory neurotransmitters, which helps dampen abnormal neuronal activity. They are not considered GABAergic agonists and have no primary effect on GABA synthesis or degradation.

Clinical uses

Gabapentin is approved as an anticonvulsant and for postherpetic neuralgia; it is also used off-label for various neuropathic pains. Pregabalin is approved for neuropathic pain from diabetic peripheral neuropathy and postherpetic neuralgia, as well as fibromyalgia, generalized anxiety disorder in some countries, and as adjunctive therapy for seizures. Mirogabalin has been studied for diabetic neuropathic pain and other neuropathic conditions in some markets. The effectiveness for some conditions varies, and treatment choices depend on local guidelines and approvals.

Pharmacokinetics and dosing

Both drugs are largely renally excreted and require dose adjustments in kidney impairment. Gabapentin is not significantly metabolized by the liver and exhibits nonlinear bioavailability at higher doses, while pregabalin has more linear pharmacokinetics. The half-life is typically several hours, leading to multiple daily doses.

Safety and considerations

Common adverse effects include dizziness, somnolence, ataxia, fatigue, and peripheral edema. Cognitive slowing, dry mouth, and weight gain can occur. There is potential for misuse and dependence, and abrupt discontinuation may cause withdrawal, so gradual tapering is advised. They can enhance CNS depression when combined with other sedatives and require caution in the elderly and during pregnancy, with regional variations in regulatory status.