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Latest revision as of 16:49, 18 September 2014

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]
delta (δ) DOR OP₁ ^(I)	δ₁, δ₂	Brain Pontine nuclei Amygdala Olfactory bulbs deep Cortex Peripheral sensory neurons	Analgesia Antidepressant effects Convulsant effects Physical dependence Perhaps of mu-opioid receptor-mediated respiratory depression
kappa (κ) KOR OP₂ ^(I)	κ₁, κ₂, κ₃	Brain Hypothalamus Periaqueductal gray Claustrum Spinal cord substantia gelatinosa Peripheral sensory neurons	Analgesia Anticonvulsant effects Dissociative & Deliriant effects Diuresis Dysphoria Miosis Neuroprotection Sedation
mu (μ) MOR OP₃ ^(I)	μ₁, μ₂, μ₃	Brain Cortex (laminae III and IV) Thalamus striosomes Periaqueductal gray Rostral ventromedial medulla Spinal cord substantia gelatinosa Peripheral sensory neurons Intestinal tract	μ₁: Analgesia Physical dependence μ₂: Respiratory depression Miosis Euphoria Reduced GI motility Physical dependence μ₃: Possible vasodilation
Nociceptin receptor NOP OP₄	ORL₁	Brain cortex Amygdala Hippocampus Septal nuclei Habenula Hypothalamus Spinal cord	Anxiety Depression Appetite Development of tolerance to μ agonists

(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.

Template:WikiDoc Sources

[pmid16402099-1] 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.

[Stein_C,_Schäfer_M,_Machelska_H_(2003)-2] 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.

[stoppain-3] 3.0 ^3.1 Fine PG, Portenoy RK (2004). "Chapter 2: The Endogenous Opioid System" (PDF). A Clinical Guide to Opioid Analgesia. McGraw Hill.

[1]

[2]

[3]

@@ Line 1: / Line 1: @@
 __NOTOC__
+{{Opioid}}
 {{CMG}}
@@ Line 5: / Line 6: @@
 ==Pharmacology==
+{{main|opioid receptor}}
+Opioids bind to specific opioid receptors in the central nervous system and in other tissues. There are three principal classes of [[opioid receptor]]s, 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: μ<sub>1</sub> and μ<sub>2</sub>. 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 receptor]]s acting on [[GABA]]ergic [[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 [[receptor antagonist|antagonist]]. For example, the [[supraspinal]] analgesic properties of the opioid agonist [[morphine]] are mediated by activation of the μ<sub>1</sub> receptor, respiratory depression and [[drug dependence|physical dependence]] (dependency) by the μ<sub>2</sub> receptor,  and sedation and spinal analgesia by the κ receptor.
+===Major subtypes===
+There are four major subtypes of opioid receptors:<ref name="pmid16402099">{{cite journal | author = Corbett AD, Henderson G, McKnight AT, Paterson SJ | title = 75 years of opioid research: the exciting but vain quest for the Holy Grail | journal = Br. J. Pharmacol. | volume = 147 Suppl 1 | issue = Suppl 1| pages = S153–62 | year = 2006 | pmid = 16402099 | doi = 10.1038/sj.bjp.0706435 | pmc = 1760732 }}</ref>
+{| class="wikitable"
+|-
+! Receptor
+! Subtypes
+! Location<ref name="Stein C, Schäfer M, Machelska H (2003)">{{cite journal | author = Stein C, Schäfer M, Machelska H | title = Attacking pain at its source: new perspectives on opioids | journal = Nat. Med. | volume = 9 | issue = 8 | pages = 1003–8 |date=August 2003 | pmid = 12894165 | doi = 10.1038/nm908 }}</ref><ref name="stoppain">{{cite book | last = Fine PG, Portenoy RK | title = A Clinical Guide to Opioid Analgesia |url= |format= |accessdate= |edition= |series= |volume= |date= |year= 2004 |month= | publisher = McGraw Hill |location= |language= |isbn= |oclc= |doi= |id= |pages= |chapter = Chapter 2: The Endogenous Opioid System |chapterurl = http://www.stoppain.org/pcd/_pdf/OpioidChapter2.pdf }}</ref>
+! Function<ref name="Stein C, Schäfer M, Machelska H (2003)"/><ref name="stoppain"/>
+ |-
+ | [[opioid receptor|delta (δ)]] <BR>DOR<BR> OP<sub>1</sub> <sup>(I)</sup> || δ<sub>1</sub>, δ<sub>2</sub> ||
+*[[Brain]]
+**[[Pons|Pontine]] nuclei
+**[[Amygdala]]
+**[[Olfactory bulbs]]
+**deep [[Cerebral cortex|Cortex]]
+* Peripheral sensory neurons
+||
+*[[Analgesia]]
+*[[Antidepressant]] effects
+* [[convulsion|Convulsant]] effects
+*[[Physical dependence]]
+* Perhaps of mu-opioid receptor-mediated respiratory depression
+ |-
+ | [[opioid receptor|kappa (κ)]] <BR>KOR<BR> OP<sub>2</sub> <sup>(I)</sup>  || κ<sub>1</sub>, κ<sub>2</sub>, κ<sub>3</sub> ||
+*[[Brain]]
+**[[Hypothalamus]]
+**[[Periaqueductal gray]]
+**[[Claustrum]]
+*[[Spinal cord]]
+**[[Substantia gelatinosa of Rolando|substantia gelatinosa]]
+* Peripheral sensory neurons
+||
+*Analgesia
+*[[Anticonvulsant]] effects
+*[[Dissociative]] & [[Deliriant]] effects
+*[[Fluid balance|Diuresis]]
+*[[Dysphoria]]
+*[[Miosis]]
+*[[Neuroprotection]]
+*[[Sedation]]
+ |-
+ | [[opioid receptor|mu (μ)]] <BR>MOR<BR> OP<sub>3</sub> <sup>(I)</sup> || μ<sub>1</sub>, μ<sub>2</sub>, μ<sub>3</sub> ||
+*[[Brain]]
+**[[Cerebral cortex|Cortex]] (laminae III and IV)
+**[[Thalamus]]
+** striosomes
+**[[Periaqueductal gray]]
+** Rostral ventromedial medulla
+*[[Spinal cord]]
+**[[Substantia gelatinosa of Rolando|substantia gelatinosa]]
+* Peripheral sensory neurons
+*[[Intestinal tract]]
+|| '''μ<sub>1</sub>''':
+*[[Analgesia]]
+*[[Physical dependence]]
+'''μ<sub>2</sub>''':
+*[[Respiratory depression]]
+*[[Miosis]]
+*[[Euphoria]]
+*Reduced [[gastrointestinal tract|GI]] [[peristalsis|motility]]
+*[[Physical dependence]]
+'''μ<sub>3</sub>''':
+*Possible vasodilation
+ |-
+ | [[Nociceptin receptor]] <BR> NOP<BR>OP<sub>4</sub> || ORL<sub>1</sub> ||
+*[[Brain]]
+**[[Cerebral cortex|cortex]]
+**[[Amygdala]]
+**[[Hippocampus]]
+**[[Septal nuclei]]
+**[[Habenula]]
+**[[Hypothalamus]]
+*[[Spinal cord]]
+||
+*Anxiety
+*Depression
+*Appetite
+*Development of tolerance to μ agonists
+|}
+<small>(I). Name based on order of discovery</small>
 ==References==