Richard Bruce Silverman (born May 12, 1946) is the Patrick G. Ryan/Aon Professor of Chemistry at Northwestern University. His group's main focus is basic and translational research into central nervous system disorders and cancer. He is known for the discovery of pregabalin, which is marketed by Pfizer under the brand name Lyrica.[1]
Silverman has been teaching and doing research at Northwestern since 1976. He became both professor of chemistry and professor of biochemistry, molecular biology, and cell biology in 1986. He has held several named professorships. He was the Arthur Andersen Professor of Chemistry from 1988 to 1996, the Charles Deering McCormick Professor of Teaching Excellence from 2001 to 2003,[4] and the John Evans Professor of Chemistry beginning from 2004 to 2015.[5] He was named the inaugural Patrick G. Ryan/Aon Professor as of September 1, 2015.[3]
Silverman has published about 400 research articles. He has been awarded 130 patents. He has written 3 books (one in the third edition): Mechanism-Based Enzyme Inactivation: Chemistry and Enzymology (CRC Press; 1988), Organic Chemistry of Drug Design and Drug Action (Academic Press; 1992, 2004, 2014), and Organic Chemistry of Enzyme-Catalyzed Reactions (Academic Press; 2000, 2002; see the Published works section, below). He is active on the editorial boards of a number of scholarly journals.[7]
Silverman is known for inventing the drug pregabalin as a possible treatment for epileptic seizures.[6] During 1988-1990, Ryszard Andruszkiewicz, a visiting research fellow, synthesized a series of molecules for Silverman.[9] One looked promising.[10] The molecule was transported into the brain, where it activated the enzyme L-glutamate decarboxylase. Silverman anticipated that the enzyme would increase production of the inhibitory neurotransmitter GABA and block convulsions.[6] Eventually, the set of molecules were sent to Parke-Davis Pharmaceuticals for testing. In addition to treating seizures, pregabalin was found to be effective in treating fibromyalgia pain, neuropathic pain, and generalized anxiety disorder.[6] It was approved by the FDA in 2004 and marketed by Pfizer (which bought Parke-Davis) under the trade name Lyrica.[6][10]
Research has shown that the mechanism of the drug is more complicated than originally anticipated.[11] In addition to its effects on GABA-AT substrate behavior, pregabalin binds to calcium channels and blocks glutamate release. GABA is potentiated, but through a different mechanism than originally suspected.[12][13]
2011 E.B. Hershberg Award for important discoveries in medicinally active substances from the American Chemical Society for the discovery of CPP-115[21]
Silverman has received numerous teaching awards from Northwestern University, including the following:
1999 E. LeRoy Hall Award for Teaching Excellence
1999 Excellence in Chemistry Education Award from the Northwestern University chapter of Alpha Chi Sigma Chemistry Fraternity
2000 Alumni Association Excellence in Teaching Award
2001-2004 Charles Deering McCormick Professor of Teaching Excellence
Philanthropy
Lyrica royalties paid to Northwestern, and a gift from Silverman himself, have supported the Silverman Hall for Molecular Therapeutics and Diagnostics at Northwestern University. Silverman Hall, which opened in 2009, was designed to be a collaborative and interdisciplinary facility housing researchers from chemistry, biology, and engineering.[6][27]
^Silverman, Richard B. (April 28, 2008). "From Basic Science to Blockbuster Drug: The Discovery of Lyrica". Angewandte Chemie International Edition. 47 (19): 3500–3504. doi:10.1002/anie.200704280. PMID18307181.
^Taylor, CP; Angelotti, T; Fauman, E (February 2007). "Pharmacology and mechanism of action of pregabalin: the calcium channel alpha2-delta (alpha2-delta) subunit as a target for antiepileptic drug discovery". Epilepsy Research. 73 (2): 137–50. doi:10.1016/j.eplepsyres.2006.09.008. PMID17126531. S2CID54254671.
