Abstract
One of the most important goals in opioid research has been the separation of analgesia and adverse effects such as respiratory depression and dependence liability. A crucial milestone was the identification of multiple opioid receptors and the demonstration of high- and low-affinity binding sites in the brain and spinal cord. Each receptor subtype is believed to mediate specific pharmacological effects. Opioid analgesia is believed to be mediated at high-affinity (μ1 receptor sites and other pharmacological effects such as cardiovascular and respiratory depression at low-affinity μ2 receptor sites [1], It has also been postulated that μ-receptor agonists will decrease tidal volume while δ-receptor agonists will decrease respiratory frequency. Since the currently available opioids do not exhibit a high specificity, they are active on both receptors. Thus, analgesia and respiratory depression are dual complimentary effects involving μ and δ-receptors [2]. This suggests that pharmacological tailoring by molecular engineering may lead to the development of a drug with selective affinity to analgesic receptors. Several receptor-selective opioids including K-agonists have been evaluated in animal and human studies.
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Rawal, N. (1990). Adverse Effects of Spinal Opioids in Acute Pain and Their Management. In: Rawal, N., Coombs, D.W. (eds) Spinal Narcotics. Current Management of Pain, vol 6. Springer, Boston, MA. https://doi.org/10.1007/978-1-4613-1609-1_5
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DOI: https://doi.org/10.1007/978-1-4613-1609-1_5
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