Once people realized that opioid drugs could cause addiction and deadly overdoses, they tried to use newer forms of opioids to treat the addiction to its parent. Morphine, about 10 times the strength of opium, was used to curb opium cravings in the early 19th century. Codeine, too, was touted as a nonaddictive drug for pain relief, as was heroin.
Those attempts were doomed to failure because all opioid drugs interact with the brain in the same way. They dock to a specific neural receptor, the mu-opioid receptor, which controls the effects of pleasure, pain relief and need.
Now scientists are trying to create opioid painkillers that give relief from pain without triggering the euphoria, dependence and life-threatening respiratory suppression that causes deadly overdoses.
The team ran 3 million possibilities through the computer and picked the 23 best candidates to test in a lab. One chemical, PZM21, seems to do what they hoped: Turn the opioid receptor on without using much beta-arrestin. They report their findings in Nature on Wednesday.
The scientists then tweaked the chemical to make it more potent and gave it to mice. The mice had pain reduction similar to that with morphine. But their breathing was more normal, and they didn’t seem to get high.