Scientists Develop New Drug Candidates Inspired by African Plant Medicine
Scientists have recently created two new potential drugs that could potentially treat addiction and depression by targeting the serotonin transporter. These drug candidates were developed based on the medicinal properties of ibogaine, a traditional African psychedelic plant medicine. Unlike ibogaine, these compounds show promising effects without the dangerous side effects associated with the plant medicine. Further testing is underway to explore the therapeutic potential of these drugs.
The study, published in the journal Cell, focused on the way ibogaine interacts with the serotonin transporter (SERT), which is also targeted by common antidepressants like Prozac. A collaborative effort between researchers from UCSF, Yale, and Duke universities led to the virtual screening of 200 million molecular structures to identify compounds that interacted with SERT in a manner similar to ibogaine.
Brian Shoichet, co-senior author and professor in the UCSF School of Pharmacy, explained that while ibogaine has shown positive effects in treating addiction, it is not a viable drug due to its side effects and the fact that it is not approved for use in the U.S. However, their new compounds were able to replicate ibogaine’s desirable effects without the drawbacks, at least in mice.
The research involved dozens of scientists from various universities who demonstrated the potential of these novel molecules. Initial identification of the compounds was done using computational docking methods to screen virtual chemical structures for binding with the protein SERT. This approach saved time and resources compared to synthesizing the compounds in the lab.
The team found that ibogaine, which is derived from the root of the iboga plant native to central Africa, interferes with various aspects of human biology, contributing to its undesirable side effects. By focusing on SERT and ibogaine’s interaction with it, the researchers were able to identify potential drug candidates that specifically target SERT.
The docking experiments led to the identification of 49 molecules, 36 of which could be synthesized. Further testing revealed that 13 of these molecules inhibited SERT. The most potent inhibitors were then tested on animal models of addiction, depression, and anxiety, showing promising results.
One of the drugs, named ‘8090, was confirmed to bind to SERT at the atomic level and inhibit it in a similar way to ibogaine. Importantly, these new compounds were found to be potent and selective, without affecting other receptors and transporters.
The team is hopeful that these new drugs could provide a better therapeutic option for patients suffering from depression and addiction. By dropping the dose significantly, these drugs could potentially have fewer side effects. The researchers have already submitted the structures of the new molecules to Sigma Aldrich, a chemical manufacturing company, for further testing by other scientists.
With millions of patients still struggling with depression and addiction, new therapies are desperately needed. This collaborative effort between experts in different fields brings hope for developing treatments that can make a difference in the lives of those affected by these disorders.