Gabapentinoids
Overview
Gabapentinoids are a class of drugs primarily used to treat seizures, neuropathic pain, and various psychiatric disorders. The class includes the active substances gabapentin and pregabalin, among others. They are structural analogs of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA), but their mechanism of action differs significantly from that of GABAergic substances.
History
The development of gabapentinoids began in the 1970s, with the synthesis of gabapentin by the pharmaceutical company Pfizer. Gabapentin was first marketed under the brand name Neurontin in 1993. Pregabalin, a more potent gabapentinoid, was later developed and marketed under the brand name Lyrica in 2004.
Pharmacology
Gabapentinoids are primarily used for their anticonvulsant and analgesic effects. They work by binding to the α2δ (alpha-2-delta) subunit of voltage-dependent calcium channels in the central nervous system (CNS). This reduces calcium influx at nerve terminals, thereby inhibiting the release of various neurotransmitters, including glutamate, substance P, and norepinephrine.
Clinical Uses
Gabapentinoids are used in the treatment of several medical conditions. These include epilepsy, neuropathic pain, fibromyalgia, and generalized anxiety disorder. They are also used off-label for a variety of other conditions, such as restless legs syndrome, bipolar disorder, and alcohol withdrawal syndrome.
Side Effects
Common side effects of gabapentinoids include dizziness, drowsiness, and peripheral edema. More serious side effects can include respiratory depression, especially when combined with other CNS depressants. There is also a risk of dependence and withdrawal symptoms with prolonged use.
Society and Culture
The recreational use of gabapentinoids has been reported, primarily for their anxiolytic and euphoric effects. This has led to increased regulation in some jurisdictions. For example, in the United States, pregabalin is classified as a Schedule V controlled substance.