New computerised drug development tools have raised hopes of identifying an ideal opioid that will provide potent central analgesia without harmful respiratory effects, be effective when used as chronic treatment, and not be addictive.
A study published online in Nature matched 3 million different compounds to the mu opioid receptor, checked more than 1 million configurations of each, examined 2,500 promising matches by eye, and finally narrowed the field to 23 compounds for experimental testing in in mice.
One of these billions of prospects stood out and led to the development of a drug called PZM21.
The drug provided comparable pain relief to morphine but the effect lasted longer. It reduced pain responses mediated in the central nervous system – the affective component – but not those mediated within the spine.
A commentary by Montreal molecular neurobiologist Professor Brigitte Kieffer said this selective activity had not previously been reported for a mu receptor agonist, and provided hope for new therapeutic options.
“The compound induced less constipation than morphine and did not modify respiratory activity,” she said.
“Strikingly, mice did not show a preference for the testing chamber in which they received PZM21 over the one in which they received saline, and the compound did not induce hyperactivity – signs of addiction-like behaviour in mice.”