Scientists in Canberra have made a major breakthrough in unlocking the secrets of how pain relief drugs work, in a discovery that could lead to powerful new treatments for conditions such as chronic pain and epilepsy.
The Australian National University's Dr Ben Corry and Lewis Martin have discovered how drug molecules attach to proteins of the nerve cell, creating the potential to redesign drugs that do not have the side effects associated with current treatments.
better understanding of how exactly pain relief drugs worked o
"The two main things we've discovered is that although we knew which proteins local anaesthetics interacted with, what we've found is exactly how and where they bind to these proteins in the body," he said.
"That's the kind of detailed knowledge we need to be able to come up with the next generation of anaesthetic drugs."
Dr Corry said the discovery created the potential to develop drugs designed to selectively target the subtly-different proteins in specific locations, such as the heart or brain.
"One of the big ones is treatment for chronic pain, which is the biggest health cost to our economy. For people with ongoing chronic pain problems, there's no effective treatment and we really just try to manage it," he said.
He added there was also potential to design drugs to better treat conditions such as epilepsy and cardiac arrhythmia without side effects.
Using a supercomputer to simulate the drug's route into the nerve cell, the pair revealed for the first time how benzocaine, a local anaesthetic, and phenytoin, an anti-epilepsy drug, enter into nerve cells and prevent pain signals from being transmitted to the brain.
Pain signals are transmitted to the brain when proteins that act as tiny gateways in nerve cell walls open, allowing sodium and potassium ions to pass through. The simulation shows that the drug’s final binding site is inside the sodium gateway protein, which blocks it and prevents the signal from being transmitted.
Drugs that block sodium channels are also used to treat nerve-signal disorders such as epilepsy or heart arrhythmia. However, current drugs target sodium channels indiscriminately throughout the body, which can lead to side effects.
Dr Corry said the time spent on the National Computational Infrastructure's supercomputer conducting the research was equivalent to running a home computer for about 340 years.
The work from ANU's Research School of Biology has been published in the latest edition of PLOS Computational Biology.
"It's pretty exciting. We haven't come out with a new range of drugs or anything like that yet, but it's the first important step in trying to work out now how we can use this in designing new drugs," Dr Corry said.