- Basic Science to Blockbuster Drug: Invention of Pregabalin (Lyrica®)
- From basic science to blockbuster drug: the discovery of Lyrica
- A Convenient Synthesis of 3-Alkyl-4-aminobutanoic Acids
- Chemoenzymatic Synthesis of (R)- and (S)-4-Amino-3-methylbutanoic Acids
- 4-Amino-3-alkylbutanoic acids as substrates for gamma-aminobutyric acid aminotransferase
- 3-Alkyl-4-aminobutyric acids: the first class of anticonvulsant agents that activates L-glutamic acid decarboxylase
- 3-alkyl GABA and 3-alkylglutamic acid analogues: two new classes of anticonvulsant agents
Pregabalin
Modulating Nerve Signals for Pain and Seizure Control
Problem
Neuropathic pain and seizure disorders affect millions of patients worldwide and can be challenging to treat effectively. Conventional pain medications often provide limited relief for nerve-related pain, while existing anticonvulsant therapies may not adequately control symptoms or can be associated with significant side effects. Patients with conditions such as diabetic neuropathy, postherpetic neuralgia, fibromyalgia, and epilepsy require therapies that offer both meaningful symptom control and long-term tolerability.
Solution
Pregabalin is a novel therapeutic agent developed to target the underlying mechanisms involved in neuropathic pain and seizure activity. Although structurally related to gamma-aminobutyric acid (GABA), pregabalin does not act directly on GABA receptors. Instead, it binds to the α2δ subunit of voltage-gated calcium channels in the central nervous system, reducing calcium influx into nerve terminals and decreasing the release of excitatory neurotransmitters involved in pain signaling and neuronal hyperexcitability.
Through this mechanism, pregabalin helps alleviate neuropathic pain, improves symptoms associated with fibromyalgia, and serves as an adjunctive treatment for partial-onset seizures. Its unique mode of action expanded the treatment options available for patients with chronic neurological disorders and established a new approach to managing neuropathic pain.
I'm deeply proud of this discovery. Hearing that pregabalin has helped patients reclaim their lives and return to a sense of normalcy is profoundly meaningful.”
— Richard Silverman, PhD
Professor, Weinberg College of Arts and Sciences
Benefits
- Neuropathic Pain Relief: Effective for diabetic neuropathy, postherpetic neuralgia, and spinal cord injury pain.
- Fibromyalgia Management: Improves pain, sleep, and overall quality of life.
- Seizure Control: Used with other medications to treat partial onset seizures.
- Rapid Onset: Patients often experience relief within days of starting therapy.
- Multiple Formulations: Available as capsules, oral solution, and extended-release tablets.
Technology & Commercialization Status
Pregabalin was discovered in the laboratory of Weinberg Professor Richard Silverman, where his research team was investigating novel GABA analogues for the treatment of neurological disorders. Through this work, the team identified pregabalin’s unique pharmacological properties and its potential as a therapy for epilepsy.
Recognizing the compound’s clinical promise, Northwestern licensed pregabalin to Parke-Davis Pharmaceuticals, which advanced the drug through preclinical development. Pregabalin was subsequently acquired by Pfizer, which advanced the drug through clinical trials and regulatory review and brought it to market under the brand name Lyrica®, securing FDA approvals for neuropathic pain, fibromyalgia, and partial-onset seizures.
Following its launch in 2004, Lyrica® became one of the most widely prescribed treatments for neuropathic pain and a commercially successful pharmaceutical product, reaching patients around the world. Today, pregabalin is available globally in both branded and generic formulations and remains an important treatment option across multiple neurological and pain-related conditions.
Northwestern Inventor
Richard B. Silverman, PhD
Patrick G. Ryan/Aon Professor in the Department of Chemistry
Weinberg College of Arts and Sciences