Opioid pharmacology
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Opioid Microchapters |
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Opioid pharmacology On the Web |
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American Roentgen Ray Society Images of Opioid pharmacology |
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Overview
Pharmacology
Opioids bind to specific opioid receptors in the central nervous system and in other tissues. There are three principal classes of opioid receptors, μ, κ, δ (mu, kappa, and delta), although up to seventeen have been reported, and include the ε, ι, λ, and ζ (epsilon, iota, lamda and zeta) receptors. σ (sigma) receptors are no longer considered to be opioid receptors as they are not reversed by naloxone, exhibit high-affinity binding for ketamine and phencyclidine and are stereoselective for dextro-rotatory isomers while the other opioid receptors are stereo-selective for laevo-rotatory isomers. In addition, there are two subtypes of μ receptor: μ1 and μ2. Another receptor of clinical importance is the opioid-receptor-like receptor 1 (ORL1), which is involved in pain responses as well as having a major role in the development of tolerance to μ-opioid agonists used as analgesics. These are all G-protein coupled receptors acting on GABAergic neurotransmission. The pharmacodynamic response to an opioid depends on which receptor it binds, its affinity for that receptor, and whether the opioid is an agonist or an antagonist. For example, the supraspinal analgesic properties of the opioid agonist morphine are mediated by activation of the μ1 receptor, respiratory depression and physical dependence (dependency) by the μ2 receptor, and sedation and spinal analgesia by the κ receptor.
Major subtypes
There are four major subtypes of opioid receptors:[1]
| Receptor | Subtypes | Location[2][3] | Function[2][3] |
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| delta (δ) DOR OP1 (I) |
δ1, δ2 |
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| kappa (κ) KOR OP2 (I) |
κ1, κ2, κ3 |
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| mu (μ) MOR OP3 (I) |
μ1, μ2, μ3 |
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μ1:
μ2: μ3:
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| Nociceptin receptor NOP OP4 |
ORL1 |
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(I). Name based on order of discovery
References
- ↑ Corbett AD, Henderson G, McKnight AT, Paterson SJ (2006). "75 years of opioid research: the exciting but vain quest for the Holy Grail". Br. J. Pharmacol. 147 Suppl 1 (Suppl 1): S153–62. doi:10.1038/sj.bjp.0706435. PMC 1760732. PMID 16402099.
- ↑ 2.0 2.1 Stein C, Schäfer M, Machelska H (August 2003). "Attacking pain at its source: new perspectives on opioids". Nat. Med. 9 (8): 1003–8. doi:10.1038/nm908. PMID 12894165.
- ↑ 3.0 3.1 Fine PG, Portenoy RK (2004). "Chapter 2: The Endogenous Opioid System" (PDF). A Clinical Guide to Opioid Analgesia. McGraw Hill.