UCSF researchers developed chemical compounds that could lead to a new generation of antidepressant and pain medications with fewer side effects than current therapies.
A new generation of pain and depression drugs with fewer adverse effects than current treatments may have been produced by UCSF researchers using chemical molecules. The research, led by Brian Shoichet, Ph.D, was detailed in separate papers published in Nature and Science, respectively.
Shoichet used the “docking” technique he developed to screen virtual libraries containing millions of molecules for candidate drugs that fit precisely into receptors of interest in both studies. Shoichet and Bryan Roth, MD, Ph.D., collaborated on the first study. They did so to create new molecules that could activate 5-HT2A, a type of serotonin receptor. Furthermore, this receptor is activated by antidepressants such as Prozac as well as psychedelics such as LSD. This has recently been shown to hold promise in the treatment of depression.
The virtual study that led to the discovery:
The researchers assembled a library of 75 million novel compounds and virtually tested them for 5HT2A activity. With the help of colleagues from Yale and Duke University, the group narrowed this library down to a few compounds. These appeared to improve mood without causing hallucinations in animal models (in animals, psychedelics produce tail-twitching).
In the second study, Shoichet collaborated with UCSF’s Allan Basbaum, Ph.D., and researchers from Freidrichs Alexander University in Germany, the Chinese University of Hong Kong, and the University of Montreal. This was done to develop pain-relieving drugs that did not cause addiction or sedation.
The group concentrated on alpha-2A adrenergic receptor activators, which Basbaum had recently identified as a promising target for new painkillers. Infact, they combed through a virtual database of 300 million molecules for those that activated alpha-2A. And they narrowed it down to just six molecules for animal testing.
They discovered that all six provided pain relief without putting the animals to sleep or causing addictive behavior. Because these drugs target an adrenergic receptor, they could theoretically be used in conjunction with opioid drugs. As a result, reducing the number of opioids required to provide relief.