A morphine-like molecule (in yellow) binds to a pocket in the mu-opiod receptor (in blue). Image from Science News. Provided by the Kobilka Lab at Stanford University.
Ever wonder how opioid drugs work their magic? Drugs like morphine, codeine and heroin? Lots of people have. And two groups of scientists, one at Stanford and one at Scripps, have made progress in figuring out how they ease pain and cause addiction. The Stanford group crystallized a morphine like molecule with the mu opioid receptor protein. Excerpted from Sceince News:
Many of today’s most powerful painkillers work by switching on one of these proteins, called the mu opioid receptor. But the relief this provides comes at a price. Derivatives of opium, such as morphine and codeine, are addictive and can cause breathing problems and constipation.
To better understand how these drugs work, an international team of researchers for the first time crystallized a small morphinelike molecule attached to a mu receptor — a technically difficult task that requires isolating the pair of molecules without unsticking them from each other. X-rays revealed how one molecule lined up with the other.
This study has limitations though: the molecule they crystallized deactivates the receptor instead of activating it like morphine or codeine, so the interactions they are looking at might not necessarily be the same interactions that are important in easy pain or causing addiction.
The Scripps group looks at a different opioid receptor, the kappa-opioid receptor. Their crystal structure reveals the binding interactions of the experimental drug JDTic with kappa-opioid receptor. This receptor is linked to stress responses moreso than pain relief, so it should tell a different story than the other.
Exciting stuff! I can’t wait to get my hands on the actual research papers.