Summary of More Powerful Than SSRIs – Scientists Develop Two New Drug Candidates That Could Treat Addiction and Depression:
Scientists have developed two new drug candidates that can potentially treat addiction and depression by targeting the serotonin transporter. These drugs were inspired by a traditional African psychedelic plant medicine called ibogaine but do not have side effects. The compounds were more powerful than SSRI antidepressants and could alleviate symptoms in mice. The research team used computational docking methods to identify molecules interacting with the serotonin transporter, like ibogaine. Further testing is underway to explore the therapeutic potential of these drugs.
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Summary:
– Scientists have developed two potential drugs for treating addiction and depression, inspired by a traditional African psychedelic plant medicine called ibogaine.
– These drug candidates mimic ibogaine’s desirable effects without its dangerous side effects.
– The compounds target the serotonin transporter (SERT) like SSRI antidepressants but with greater potency.
– The virtual screening of 200 million molecular structures identified these promising molecules.
– Further testing is underway to explore their therapeutic potential.
In recent groundbreaking research, scientists have developed two new drug candidates with immense potential to treat addiction and depression. These compounds, inspired by a traditional African psychedelic plant medicine called ibogaine, target the serotonin transporter (SERT) and mimic its effects without the dangerous side effects associated with ibogaine.
The study, led by a collaborative research team from the University of California, San Francisco (UCSF), Yale University, and Duke University, was recently published in Cell. The researchers virtually screened 200 million molecular structures to identify compounds that interacted with SERT, like ibogaine.
Brian Shoichet, Ph.D., co-senior author and professor at the UCSF School of Pharmacy, explained the motivations behind the research. “Some people swear by ibogaine for treating addiction, but it isn’t a perfect drug. He said that it has bad side effects and is not approved for use in the U.S.,” he said. “Our compounds mimic just one of ibogaine’s many pharmacological effects and still replicate its most desirable effects on behavior, at least in mice.”
The discovery of these novel molecules involved an intricate process known as docking. Scientists systematically tested virtual chemical structures for their ability to bind with SERT, eliminating the need to synthesize and test them in the lab. This approach significantly accelerated the search for potential drug leads.
Initially, the virtual screening narrowed down the library from 200 million to just 49 molecules, 36 of which could be synthesized. Further testing revealed 13 compounds inhibited SERT, demonstrating their potential therapeutic value. To prioritize the most promising molecules for further optimization, the researchers organized virtual-reality-guided “docking parties,” where teams of experts evaluated the molecular structures.
The two most potent SERT inhibitors were shared with other researchers for rigorous testing on animal models of addiction, depression, and anxiety. Astonishingly, these drugs exhibited unprecedented potency compared to even paroxetine (Paxil), a well-known SSRI antidepressant.
Aashish Manglik, MD, Ph.D., an expert in cryo-electron microscopy (cryo-EM), confirmed that one of the drug candidates, referred to as ‘8090, fit into SERT at the atomic level as predicted by the computational models. Both drugs inhibited SERT, similar to ibogaine, but without the psychedelic effects. Importantly, they showed no spillover impacts on many other receptors and transporters, making them highly selective and less likely to cause side effects.
“With this sort of potency, we hope to have a better therapeutic window without side effects,” said Allan Basbaum, Ph.D., one of the researchers involved in the study. “Dropping the dose almost 200-fold could make a big difference for patients.”
The structures of these new molecules have been submitted to Sigma Aldrich, a chemical manufacturing company, to make them available for further testing by other scientists. Meanwhile, Brian Shoichet continues his search for even more specific molecules that may hold the key to targeted and effective treatments for addiction and depression.
Developing these potential drugs is a significant breakthrough for millions of patients worldwide suffering from depression and addiction. Traditional treatments like SSRIs have limitations, and alternative therapeutic options are urgently needed. By drawing inspiration from traditional African medicine, scientists have opened up new possibilities for treating these debilitating disorders.
The collaborative nature of this research, involving experts from diverse fields, exemplifies the power of interdisciplinary teamwork. “This is how science should be done,” remarked Allan Basbaum. “We took a group with expertise in disparate fields and came up with something that might make a difference.”
As research on these drug candidates progresses, there is renewed hope for a brighter future in treating addiction and depression. The groundbreaking work of these scientists highlights the endless possibilities when ancient wisdom meets modern medicine, all in the pursuit of improving the lives of those suffering.
