Scientists are chasing a new lead on a class of drugs that may one day fight both pain and opioid addiction. It's still early days, but researchers report that they've discovered a new small molecule that binds selectively to a long-targeted enzyme, halting its role in pain and addiction while not interfering with enzymes critical to healthy cell function. The newly discovered compound isn't likely to become a medicine any time soon. But it could jumpstart the search for other binders that could do the job.
Pain and addiction have many biochemical roots, which makes it difficult to treat them without affecting other critical functions in cells. Today, the most potent painkillers are opioids, including heroin, oxycodone, and hydrocodone. In addition to interrupting pain, they inhibit enzymes known as adenylyl cyclases (ACs) that convert cells' energy currency, ATP, into a molecule involved in intracellular chemical communication known as cyclic AMP (cAMP). Chronic opioid use can make cells increase the activity of ACs to compensate, causing cAMP levels to skyrocket. When opioid users try to stop using, their cAMP levels remain high, and drugs that reduce those levels—like buprenorphine—have unwanted side effects.