The representative drugs, which are early central κ-opioid receptor (KOR) agonists, include U-50488, ICI-199441, spiradoline (U-6266E) and enadoline, that produce good analgesic activity without morphine-like side effects (i.e., respiratory depression, constipation, addiction and tolerance), and are able to antagonize the drug dependence caused by μ receptor activation (6). Here, OPRK1 is linked to respiratory depression.