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The Therapeutic Potential of κ-Opioids for Treatment of Pain and Addiction

2010; Springer Nature; Volume: 36; Issue: 1 Linguagem: Inglês

10.1038/npp.2010.137

1740-634X

Charles Chavkin,

Pain Mechanisms and Treatments

When the κ-subtype of opioid receptor was first distinguished, there was tremendous interest in developing analgesics that would provide pain-relief without activating the reward pathways stimulated by morphine-like μ-opioids. A nonaddictive opioid has been a holy grail of medicinal chemistry ever since Friedrich Serturner isolated morphine from opium in 1804. Selective κ-agonists were developed, but quickly found to produce different problems including dysphoria, diuresis, and constipation. In addition, their maximal analgesic effects were weaker than μ-opioids in rodents. But interest in κ-opioids as therapeutic tools did not completely die; Shippenberg and colleagues found that κ-agonists reduced the rewarding effects of co-administered addictive drugs; κ-opioid analgesia using pentazocine was seen as an alternative for pain control in people with a risk of drug abuse; and κ-agonists entered clinical trials for the treatment of pain and itch (see Millan, 1990).