Pregabalin is structurally similar to gamma-aminobutyric acid (GABA) - an inhibitory neurotransmitter. It may be used to manage neuropathic pain, postherpetic neuralgia, and fibromyalgia among other conditions. Although as per the FDA Label the mechanism of action has not been definitively defined, there is evidence that Pregabalin exerts its effects by binding to the ?2? subunit of voltage-dependent calcium channels. It may have dependence liability if misused but the risk appears to be highest in patients with current or past substance use disorders.
Pregabalin is indicated for the management of neuropathic pain associated with diabetic peripheral neuropathy, postherpetic neuralgia, fibromyalgia, neuropathic pain associated with spinal cord injury, and as adjunctive therapy for the treatment of partial-onset seizures in patients 1 month of age and older.
Although the structure of Pregabalin is similar to gamma-aminobutyric acid (GABA), it does not bind to GABA receptors. Instead, it binds the alpha2-delta subunit of presynaptic voltage-gated calcium channels in the central nervous system. Pregabalin does not modulate dopamine receptors, serotonin receptors, opiate receptors, sodium channels or cyclooxygenase activity.
Although the mechanism of action has not been fully elucidated, studies involving structurally related drugs suggest that presynaptic binding of Pregabalin to voltage-gated calcium channels is key to the antiseizure and antinociceptive effects observed in animal models.
By binding presynaptically to the alpha2-delta subunit of voltage-gated calcium channels in the central nervous system, Pregabalin modulates the release of several excitatory neurotransmitters including glutamate, substance-P, norepinephrine, and calcitonin gene related peptide. In addition, Pregabalin prevents the alpha2-delta subunit from being trafficked from the dorsal root ganglia to the spinal dorsal horn, which may also contribute to the mechanism of action.
Although Pregabalin is a structural derivative of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA), it does not bind directly to GABA or benzodiazepine receptors.
After oral dosing administered in the fasted state, Pregabalin absorption is rapid, and extensive.8 Pregabalin oral bioavailability is reported to be ?90% regardless of the dose.
Less than 2% of Pregabalin is metabolized and it is excreted virtually unchanged in the urine.
Pregabalin is almost exclusively eliminated in the urine.
The elimination half-life of Pregabalin is 6.3 hours.
DOSAGE AND ADMINISTRATION
Initial: 50 mg orally every 8 hours Maintenance: May increase to 100 mg orally every 8 hours within 1 week, as needed; not to exceed 300 mg/day.
