Glutamatergic Agents Across a Broad Range of Applications
Yale researchers were among the first to identify ketamine – a drug best known for its use by club goers for its hallucinogenic effects—as a promising therapy for patients with treatment-resistant depression and anxiety. The finding was a major discovery that revealed a new pathway for treating these neuropsychiatric disorders. Rather than acting on the brain’s levels of serotonin, norepinephrine and dopamine as other mood and anxiety drugs do, ketamine worked on regulating levels of a neurotransmitter called glutamate. “It’s a completely different approach,” says Gerard Sanacora M.D., professor of psychiatry and director of the Yale Depression Research Program. “It’s an all-purpose approach that’s physiologically-based across diagnostic categories.” The Yale group’s seminal work on ketamine was first published in Berman et al. 2000 and has led to numerous lines of research exploring glutamatergic mechanisms in neuropsychiatric disorders.
Having witnessed successful results using ketamine on depressed patients, the Yale researchers began focusing on other ways to modulate brain glutamate without the dissociative effects of ketamine. John Krystal M.D., Chairman of the Department of Psychiatry at Yale and Chief of Psychiatry at Yale-New Haven Hospital, mentored a next generation of Yale researchers to further expand the exploration of other glutamate modulating agents in neuropsychiatric disorders. Vlad Coric M.D., Associate Clinical Professor of Psychiatry at Yale, was the first to demonstrate anxiolytic properties of the glutamate modulating agent Riluzole in patients with treatment-resistant OCD. With colleagues Drs. Christopher Pittenger and Michael Bloch at the Yale OCD Research Clinic, the group expanded their work to explore the therapeutic potential of other glutamate modulating agents.
Drs. Krystal, Sanacora and Coric turned to the Yale Office of Cooperative Research (OCR) to file the necessary patents and begin the process of translating their research into new therapies. What ultimately emerged from the co-inventors research was the startup Biohaven Pharmaceutical Holding Company, Ltd, a company dedicated to developing a new generation of drugs for treating targeted diseases by regulating glutamate. Integral to the company’s formation was contributions by seasoned drug developer Declan Doogan, M.D., former Senior VP Head of World Drug Development at Pfizer, and Robert Berman, M.D. who lead Bristol-Myers Squib;s ABILIFY program in attaining a first-cycle FDA approval for adjunctive use in major depressive disorder.