Last reviewed 2026-04-20 · How we verify

Lyrica (Pregabalin)

Pregabalin binds alpha-2-delta subunit of voltage-gated calcium channels in CNS.

Pregabalin is an anticonvulsant and analgesic that binds the alpha-2-delta subunit of voltage-gated calcium channels to reduce nociceptive neurotransmitter release and modulate pain pathways. It is indicated for diabetic peripheral neuropathy, postherpetic neuralgia, partial-onset seizures, fibromyalgia, and spinal cord injury neuropathic pain. Primary risks include hypersensitivity reactions and additive CNS depression with opioids, benzodiazepines, or alcohol; renal excretion requires monitoring in renal impairment. Pregabalin remains a widely used agent with established efficacy across multiple neuropathic pain and seizure indications.

At a glance

Mechanism of action

Pregabalin binds with high affinity to the alpha-2-delta site, an auxiliary subunit of voltage-gated calcium channels in central nervous system tissues. Although the mechanism has not been fully elucidated, binding to this subunit appears involved in pregabalin's anti-nociceptive and antiseizure effects. In animal models of nerve damage, pregabalin reduces calcium-dependent release of pro-nociceptive neurotransmitters in the spinal cord, possibly by disrupting alpha-2-delta containing calcium channel trafficking and/or reducing calcium currents. Evidence suggests anti-nociceptive activities may also be mediated through interactions with descending noradrenergic and serotonergic pathways from the brainstem that modulate pain transmission in the spinal cord. Notably, pregabalin does not bind directly to GABA-A, GABA-B, or benzodiazepine receptors, does not block sodium channels, is not active at opiate receptors, and does not alter cyclooxygenase enzyme activity. However, prolonged application in cultured neurons increases GABA transporter protein density and functional GABA transport rate.

Approved indications

• Neuropathic pain associated with diabetic peripheral neuropathy
• Postherpetic neuralgia
• Adjunctive therapy for partial-onset seizures
• Fibromyalgia
• Neuropathic pain associated with spinal cord injury

Common side effects

• acromion fracture
• Hypotension
• buccal ulcer
• Nausea
• dizziness and/or somnolence
• Dyspnea

Drug interactions

• Oxycodone
• Lorazepam
• Ethanol
• Carbamazepine, valproic acid, lamotrigine, phenytoin, phenobarbital, topiramate

Key clinical trials

• Effects of 2-Aticyto Complex and D-Ribose on Pain and Clinical Course in Patients With Fibromyalgia (NA)
• Evaluation of Efficacy and Safety of VX-993 for Pain Associated With Diabetic Peripheral Neuropathy (PHASE2)
• Effect of Pregabalin on the Postoperative Analgesia in RFA of Focal Lesions in the Liver (PHASE4)
• Efficacy and Safety of Mirogabalin in Diabetic Peripheral Neuropathic Pain (PHASE4)
• Transcranial Magnetic Stimulation Therapy in Neuropathic Painful Spinal Cord Injury Patients (NA)
• Effect of Low-dose Pregabalin Retard (82.5 mg) Versus Standard-dose Pregabalin Retard (165 mg) on Postoperative Pain and Opioid Consumption After Elective Laparoscopic Abdominal Surgery: a Randomized, Double-blind, Controlled Trial (NA)
• The Efficacy and Safety of Pregabalin and Mirogabalin in Patients With Fibromyalgia (NA)
• A Study of HRS-2129 in Patients With Diabetic Peripheral Neuropathic Pain (PHASE1)

Patents

Primary sources

Every claim on this page is sourced from regulatory or scientific primary sources. See our editorial policy for full methodology.