Pregabalin

Abstract

Pregabalin, the pharmacologically active S-enantiomer of 3-aminomethyl-5-methyl-hexanoic acid, has a similar pharmacological profile to that of its developmental predecessor gabapentin, but showed greater analgesic activity in rodent models of neuropathic pain. The exact mechanism of action of pregabalin is unclear, although it may reduce excitatory neurotransmitter release by binding to the alpha2-delta protein subunit of voltage-gated calcium channels. Oral pregabalin 150-600 mg/day, administered twice or three times daily, was superior to placebo in relieving pain and improving pain-related sleep interference in three randomised, double-blind, placebo-controlled, multicentre studies of 8-13 weeks' duration in a total of 776 evaluable patients with postherpetic neuralgia (PHN). Weekly mean pain scores (primary endpoint; assessed in all three studies) and weekly mean sleep interference scores (assessed in two studies) were significantly improved at 1 week. In two studies, significant improvements in daily mean pain scores were apparent on the first or second day of treatment with pregabalin administered three times daily. Pregabalin was generally well tolerated when force-titrated over 1 week to fixed dosages (maximum 600 mg/day) in clinical trials that enrolled most elderly PHN patients. Dizziness, somnolence and peripheral oedema of mild-to-moderate intensity were the most common adverse events.