Chemistry of Life Processes Institute faculty member Richard Silverman (chemistry and molecular biosciences) has developed a new compound, OV329, that could provide many people relief from drug addiction. The story of OV329 recently received a write up in Science.

OV329 works by suppressing the signals of brain’s dopamine reward system. Spikes in the level of dopamine, a neurotransmitter, are present in addiction (Juncosa et al. J Am Chem Soc. 2018 Feb 14;140(6):2151-2164).

“Addiction occurs when drugs or other pleasurable stimuli hijack the brain’s normal reward system, which has evolved to reinforce beneficial behaviors, such as eating food and having sex. Such behaviors produce spikes in the release of dopamine in brain regions that are associated with motivation. Opioids and other drugs activate other neural receptors and create a euphoric high, which in turn triggers addiction-forming dopamine spikes.”

OV329 blocks the GABA-AT enzyme from breaking down the GABA neurotransmitter. GABA is an inhibitory neurotransmitter that suppresses the firing of some neurons, including dopamine-releasing neurons.  Increased levels of GABA in the brain can block the brain’s reward system.

When researchers treated cocaine- or nicotine-addicted rats with OV329, the animals’ dopamine spikes neutralized and they stopped self-administration of the drugs.

The hope is that OV329 can be brought to market to break the addiction cycle in humans. The compound has been licensed to Ovid Therapeutics, in New York City, for further development.

Story published in Science and written by Robert F. Service. 

Silverman is a resident faculty member in the Chemistry of Life Processes Institute, with his laboratory situated in the Richard and Barbara Silverman Hall for Molecular Therapeutics and Diagnostics. He is a member of the CLP Faculty Executive Committee and he is the principal investigator/director of the NIH-funded CLP Predoctoral Training Program.  His earlier work on new therapeutics for Parkinson’s disease was supported by a pilot grant from the CLP Cornew Innovation Fund.