Novel Strategies for Accelerating Non-opioid Drug Discovery
Abstract
The central problem addressed by our proposal is our societal dependence on opioid drugs as the primary therapy for severe pain. Opioid drugs include drugs like morphine, oxycodone, and hydrocodone that are often prescribed for the severe pain that accompanies a serious injury or for post-surgical pain. However, the broad use of opioid drugs for pain management has resulted in a broad range of societal problems, creating an urgent need to phase out the pervasive use of opioid drugs for pain. Opioids have many well-known problems including drug abuse, addiction, overdose, tolerance, and many dangerous and unpleasant side effects. The best solution to the negative effects on society is to treat pain through a diverse new set of effective non-opioid drugs. However, very few new pain drugs have been introduced into clinical medicine in recent decades. The current major classes of pain drugs were discovered from natural sources long ago. The opioid drugs were derived from morphine, originally isolated from the opium poppy. The non-steroidal anti-inflammatory drugs were inspired by aspirin, isolated from other plant sources, such as willow bark. Prior to the isolation of their analgesic compounds in the 19th century, these medicinal plants and plant extracts were used since antiquity to treat pain. Modern drug discovery methods have done little to add to the repertoire of therapeutic pain drugs. We propose to return to natural products as the source of the next generation of pain therapeutics, with a new focus on marine organisms, which have largely been inaccessible to humans as sources of traditional pain therapies, in contrast to plant sources that have been explored extensively throughout history. It is notable that one of the only novel pain drugs to be introduced to human patients in recent decades was discovered from a marine source in the laboratory of the program’s Principal Investigator, Dr. Olivera. Our proposal encompasses five independent but highly synergistic projects. Project 1 aims to identify new molecular and cellular targets for pain drug discovery. Projects 2 and 3 propose to compile and screen large collections of natural products for their ability to stop, prevent, or reverse the events that result in chronic or non-normal pain. Projects 4 and 5 propose focused pain drug-discovery efforts for non-opioid drug targets. They will also utilize the resources of Projects 1, 2, and 3 to facilitate their drug discovery. Projects 2 and 5 already have potential pain drugs that they can advance through preclinical testing and eventually to clinical testing, possibly in a relatively short time frame. All of the projects will use a common drug testing core that has the potential to create genuine synergies between all projects and all scientists involved in this research program. We believe that our research program will discover new and important non-opioid pain drugs.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Oct 29, 2018
- Source ID
- W81XWH1710413
Entities
People
- Baldomero Olivera
Organizations
- United States Army
- University of Utah