Abstract
μ-Opioid receptor agonists are a mainstay of clinical analgesia, despite the significant unwanted effects and dependence liability associated with drugs like morphine. The quest for opioids that produce analgesia with fewer undesirable effects has lead to the putative identification of multiple opioid receptor subtypes, despite the identification of only four opioid-related receptor genes. One such putative receptor subtype is the κ 3 receptor, activation of which supposedly produces analgesia in animals. In the present issue of this Journal, Olianas and co-workers have demonstrated that the prototypic κ 3 agonist naloxone benzoylhydrazone is actually a partial agonist at the cloned μ, δ, and κ opioid receptors and an antagonist at opioid-like NOP receptors. Together with a recent study that showed that high-affinity naloxone benzoylhydrazone binding is abolished in triple μ/δ/κ receptor knockout mice, the present study provides strong evidence that in vivo effects attributed to κ 3 receptor activation probably just reflect the combined actions of a particularly nonselective opioid drug. Indeed, molecular identification of any of the proposed subtypes of μ, δ, and κ opioid receptors has proven elusive, suggesting that it is perhaps time to retire the notion of opioid receptor subtypes until definitive evidence for their existence is provided.
Original language | English |
---|---|
Pages (from-to) | 349-350 |
Number of pages | 2 |
Journal | British Journal of Pharmacology |
Volume | 147 |
Issue number | 4 |
DOIs | |
Publication status | Published - Feb 2006 |
Externally published | Yes |
Keywords
- Analgesia
- Naloxone benzoylhydrazone
- Pharmacological fantasy
- Receptor knock out