Drugs that act on various opioid receptors in the brain have proven invaluable for treating pain and remain mainstays in pain relief. But all opiate drugs studied to date have a number of drawbacks—most notably their reinforcing effects and physical dependence that underlie their addictive potential, as well as their tendency to stop movement through the intestines (constipation) and their dangerous effect of depressing respiration. Recent research has revealed that some opioid receptors are more complex and have a wider array of variants than once thought, and new research is focusing on finding compounds that might relieve pain without causing other side effects by binding to very specific receptor variants. In a new study, researchers using mice genetically modified to express only limited types of opioid receptors have isolated such a compound, called iodobenzoylnaltrexamide or IBNtxA. This compound—which was derived from the drug naltrexone, widely used in the treatment of alcohol and opioid dependence—powerfully relieved pain in the animals without affecting their respiration and without being rewarding (or addictive), and it produced only minimal constipation. The compound targets a particular shortened, or truncated, variant of a type of opioid receptor called the mu-opioid receptor. IBNtxA is not a perfect drug, according to the authors of the study, but its discovery proves that pain relief can indeed be decoupled from classic opiate side effects and greatly deepens our understanding of the body’s opioid pain-relief system.
J Med Chem. 2012 Jul 26;55(14):6352-62. Epub 2012 Jul 16. http://www.ncbi.nlm.nih.gov/pubmed/22734622