Those animals with more active forms of the gene had higher numbers
of mu receptors in their tissues — and higher tolerances for pain.
The scientists then added two atoms that made its affinity for
the mu receptor 40 times stronger.
Using computer simulations called molecular docking, team members screened more than 3 million molecules to find some 2,500 that fit
the mu receptor like a perfectly cut key in a lock.
Now, after more than 15 years of research, Maryland's Andrew Coop has patented a compound — UMB 425 — that binds to
the mu receptor to deliver pain relief, while simultaneously blocking the delta receptor.
In 2012, a co-author of the study, Nobel Laureate Brian Kobilka, determined the physical structure of
the mu receptor, and with its exact size and shape in hand, an international team of scientists sought to create a compound that would fit it, conferring analgesia in a way that would trigger fewer side effects than opioids.
Opioids work to activate this pathway via
the mu receptor, and decrease the signal coming in from the painful site.
But it's
the mu receptor that is primarily responsible for opioids» analgesic effects, and drugs that fit it snugly launch a cascade of chemical changes in nerve cells that slow down the transmission of pain messages to the spinal cord and the brain.
Tramadol, an atypical opioid drug, weakly binds to
mu receptors.
It binds to
mu receptors but has only partial clinical effects, making it appropriate for mild to moderate pain, but not severe pain.
Fentanyl binds only
the mu receptor and does so approximately 75 to 100 times stronger than morphine, making it an excellent choice for pain relief.
Buprenorphine, an opiate, is
a mu receptor.