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Wikipedia

Alpha-2 adrenergic receptor

January 22, 2023

See also: Adrenergic receptor

The alpha-2 (α2) adrenergic receptor (or adrenoceptor) is a G protein-coupled receptor (GPCR) associated with the Gi heterotrimeric G-protein. It consists of three highly homologous subtypes, including α2A-, α2B-, and α2C-adrenergic. Some species other than humans express a fourth α2D-adrenergic receptor as well.[1] Catecholamines like norepinephrine (noradrenaline) and epinephrine (adrenaline) signal through the α2-adrenergic receptor in the central and peripheral nervous systems.

Cellular localization

The α2A adrenergic receptor is localised in the following central nervous system (CNS) structures:[2]

Whereas the α2B adrenergic receptor is localised in the following CNS structures:[2]

  • Olfactory system
  • Thalamus
  • Pyramidal layer of the hippocampus
  • Cerebellar Purkinje layer

and the α2C adrenergic receptor is localised in the CNS structures:[2]

  • Midbrain
  • Thalamus
  • Amygdala
  • Dorsal root ganglia
  • Olfactory system
  • Hippocampus
  • Cerebral cortex
  • Basal ganglia
  • Substantia nigra
  • Ventral tegmentum

Effects

The α2-adrenergic receptor is classically located on vascular prejunctional terminals where it inhibits the release of norepinephrine (noradrenaline) in a form of negative feedback.[3] It is also located on the vascular smooth muscle cells of certain blood vessels, such as those found in skin arterioles or on veins, where it sits alongside the more plentiful α1-adrenergic receptor.[3] The α2-adrenergic receptor binds both norepinephrine released by sympathetic postganglionic fibers and epinephrine (adrenaline) released by the adrenal medulla, binding norepinephrine with slightly higher affinity.[4] It has several general functions in common with the α1-adrenergic receptor, but also has specific effects of its own. Agonists (activators) of the α2-adrenergic receptor are frequently used in anaesthesia where they affect sedation, muscle relaxation and analgesia through effects on the central nervous system (CNS).[5]

General

Common effects include:

Individual

Individual actions of the α2 receptor include:

Signaling cascade

The α subunit of an inhibitory G protein - Gi dissociates from the G protein,[16] and associates with adenylyl cyclase. This causes the inactivation of adenylyl cyclase, resulting in a decrease of cAMP produced from ATP, which leads to a decrease of intracellular cAMP. PKA is not able to be activated by cAMP, so proteins such as phosphorylase kinase cannot be phosphorylated by PKA. In particular, phosphorylase kinase is responsible for the phosphorylation and activation of glycogen phosphorylase, an enzyme necessary for glycogen breakdown. Thus in this pathway, the downstream effect of adenylyl cyclase inactivation is decreased breakdown of glycogen.

The relaxation of gastrointestinal tract motility is by presynaptic inhibition,[13] where transmitters inhibit further release by homotropic effects.

Agonists

Partial agonists
Antagonists
Binding affinity (Ki in nM) and clinical data on a number of alpha-2 ligands[23][24][25][26]
Drug α1A α1B α1D α2A α2B α2C Indication(s) Route of Administration Bioavailability Elimination half-life Metabolising enzymes Protein binding
Agonists
Clonidine 316.23 316.23 125.89 42.92 106.31 233.1 Hypertension, ADHD, analgesia, sedation Oral, epidural, transdermal 75-85% (IR), 89% (XR) 12-16 h CYP2D6 20-40%
Dexmedetomidine 199.53 316.23 79.23 6.13 18.46 37.72 Procedural and ICU sedation IV 100% 6 minutes 94%
Guanfacine ? ? ? 71.81 1200.2 2505.2 Hypertension, ADHD Oral 80-100% (IR), 58% (XR) 17 h (IR), 18 h (XR) CYP3A4 70%
Xylazine ? ? ? 5754.4 3467.4 >10000 Veterinary sedation ? ? ? ? ?
Xylometazoline ? ? ? 15.14 1047.13 128.8 Nasal congestion Intranasal ? ? ? ?
Antagonists
Asenapine 1.2 ? ? 1.2 0.32 1.2 Schizophrenia, bipolar disorder Sublingual 35% 24 h CYP1A2 & UGT1A4 95%
Clozapine 1.62 7 ? 37 25 6 Treatment-resistant schizophrenia Oral 50-60% 12 h CYP1A2, CYP3A4, CYP2D6 97%
Mianserin 74 ? ? 4.8 27 3.8 Depression Oral 20% 21-61 h CYP3A4 95%
Mirtazapine 500 ? ? 20 ? 18 Depression Oral 50% 20-40 h CYP1A2, CYP2D6, CYP3A4 85%

Agonists

Main article: alpha-adrenergic agonist

Norepinephrine has higher affinity for the α2 receptor than has epinephrine, and therefore relates less to the latter's functions.[13] Nonselective α2 agonists include the antihypertensive drug clonidine,[13] which can be used to lower blood pressure and to reduce hot flashes associated with menopause. Clonidine has also been successfully used in indications that exceed what would be expected from a simple blood-pressure lowering drug: it has recently shown positive results in children with ADHD who have tics resulting from the treatment with a CNS stimulant drug, such as Adderall XR or methylphenidate;[27] clonidine also helps alleviate symptoms of opioid withdrawal.[28] The hypotensive effect of clonidine was initially attributed through its agonist action on presynaptic α2 receptors, which act as a down-regulator on the amount of norepinephrine released in the synaptic cleft, an example of autoreceptor. However, it is now known that clonidine binds to imidazoline receptors with a much greater affinity than α2 receptors, which would account for its applications outside the field of hypertension alone. Imidazoline receptors occur in the nucleus tractus solitarii and also the centrolateral medulla. Clonidine is now thought to decrease blood pressure via this central mechanism. Other nonselective agonists include dexmedetomidine, lofexidine (another antihypertensive), TDIQ (partial agonist), tizanidine (in spasms, cramping) and xylazine. Xylazine has veterinary use.

In the European Union, dexmedetomidine received a marketing authorization from the European Medicines Agency (EMA) on August 10, 2012, under the brand name of Dexdor.[29] It is indicated for sedation in the ICU for patients needing mechanical ventilation.

In non-human species this is an immobilizing and anesthetic drug, presumptively also mediated by α2 adrenergic receptors because it is reversed by yohimbine, an α2 antagonist.

α2A selective agonists include guanfacine (an antihypertensive) and Brimonidine (UK 14,304).

(R)-3-nitrobiphenyline is an α2C selective agonist as well as being a weak antagonist at the α2A and α2B subtypes.[30][31]

Antagonists

Main article: alpha blocker

Nonselective α blockers include, A-80426, atipamezole, phenoxybenzamine, efaroxan, idazoxan*[13](experimental),[32] and SB-269,970.

Yohimbine*[13] is a relatively selective alpha-2 blocker that has been investigated as a treatment for erectile dysfunction.

Tetracyclic antidepressants mirtazapine and mianserin are also potent α antagonists with mirtazapine being more selective for α2 subtype (~30-fold selective over α1) than mianserin (~17-fold).

α2A selective blockers include BRL-44408 and RX-821,002.

α2B selective blockers include ARC-239 and imiloxan.

α2C selective blockers include JP-1302 and spiroxatrine, the latter also being a serotonin 5-HT1A antagonist.

See also

References

  1. ^ Ruuskanen JO, Xhaard H, Marjamäki A, Salaneck E, Salminen T, Yan YL, Postlethwait JH, Johnson MS, Larhammar D, Scheinin M (January 2004). "Identification of duplicated fourth alpha2-adrenergic receptor subtype by cloning and mapping of five receptor genes in zebrafish". Molecular Biology and Evolution. 21 (1): 14–28. doi:10.1093/molbev/msg224. PMID 12949138.
  2. ^ a b c Saunders, C; Limbird, LE (November 1999). "Localization and trafficking of alpha2-adrenergic receptor subtypes in cells and tissues". Pharmacology & Therapeutics. 84 (2): 193–205. doi:10.1016/S0163-7258(99)00032-7. PMID 10596906.
  3. ^ a b c Cardiovascular Physiology, 3rd Edition, Arnold Publishers, Levick, J.R., Chapter 14.1, Sympathetic vasoconstrictor nerves
  4. ^ Boron, Walter F. (2012). Medical Physiology: A Cellular and Molecular Approach. p. 360.
  5. ^ a b c Khan, ZP; Ferguson, CN; Jones, RM (February 1999). "alpha-2 and imidazoline receptor agonists. Their pharmacology and therapeutic role". Anaesthesia. 54 (2): 146–65. doi:10.1046/j.1365-2044.1999.00659.x. PMID 10215710.
  6. ^ Goodman Gilman, Alfred. Goodman & Gilman's The Pharmacological Basis of Therapeutics. Tenth Edition. McGraw-Hill (2001): Page 140.
  7. ^ Woodman OL, Vatner SF (1987). "Coronary vasoconstriction mediated by α1- and α2-adrenoceptors in conscious dogs". Am. J. Physiol. 253 (2 Pt 2): H388–93. doi:10.1152/ajpheart.1987.253.2.H388. PMID 2887122.
  8. ^ Sun, D.; Huang, A.; Mital, S.; Kichuk, M. R.; Marboe, C. C.; Addonizio, L. J.; Michler, R. E.; Koller, A.; Hintze, T. H.; Kaley, G. (2002). "Norepinephrine elicits beta2-receptor-mediated dilation of isolated human coronary arterioles". Circulation. 106 (5): 550–555. doi:10.1161/01.CIR.0000023896.70583.9F. PMID 12147535.
  9. ^ a b Basic & Clinical Pharmacology, 11th Edition, McGrawHill LANGE, Katzung Betram G.; Chapter 9. Adrenoceptor Agonists & Sympathomimetic Drugs
  10. ^ Elliott J (1997). "Alpha-adrenoceptors in equine digital veins: evidence for the presence of both α1 and α2-receptors mediating vasoconstriction". J. Vet. Pharmacol. Ther. 20 (4): 308–17. doi:10.1046/j.1365-2885.1997.00078.x. PMID 9280371.
  11. ^ Sagrada A, Fargeas MJ, Bueno L (1987). "Involvement of α1 and α2 adrenoceptors in the postlaparotomy intestinal motor disturbances in the rat". Gut. 28 (8): 955–9. doi:10.1136/gut.28.8.955. PMC 1433140. PMID 2889649.
  12. ^ a b Arnsten, AFT (26 July 2007). "Alpha-2 Agonists in the Treatment of ADHD". Medscape Psychiatry. WebMD. Retrieved 13 November 2013.
  13. ^ a b c d e f g Rang, H. P. (2003). Pharmacology. Edinburgh: Churchill Livingstone. ISBN 978-0-443-07145-4. Page 163
  14. ^ Wright EE, Simpson ER (1981). "Inhibition of the lipolytic action of beta-adrenergic agonists in human adipocytes by alpha-adrenergic agonists". J. Lipid Res. 22 (8): 1265–70. doi:10.1016/S0022-2275(20)37319-3. PMID 6119348.
  15. ^ a b Fitzpatrick, David; Purves, Dale; Augustine, George (2004). "Table 20:2". Neuroscience (Third ed.). Sunderland, Mass: Sinauer. ISBN 978-0-87893-725-7.
  16. ^ Kou Qin; Pooja R. Sethi; Nevin A. Lambert (August 2008). "Abundance and stability of complexes containing inactive G protein-coupled receptors and G proteins". The FASEB Journal. 22 (8): 2920–2927. doi:10.1096/fj.08-105775. PMC 2493464. PMID 18434433.
  17. ^ "Methamphetamine – Targets". DrugBank. University of Alberta. 8 February 2013. Retrieved 31 December 2013.
  18. ^ Spencer RC, Devilbiss DM, Berridge CW (June 2015). "The Cognition-Enhancing Effects of Psychostimulants Involve Direct Action in the Prefrontal Cortex". Biol. Psychiatry. 77 (11): 940–950. doi:10.1016/j.biopsych.2014.09.013. PMC 4377121. PMID 25499957. The procognitive actions of psychostimulants are only associated with low doses... cognition-enhancing effects of psychostimulants involve the preferential elevation of catecholamines in the PFC and the subsequent activation of norepinephrine α2 and dopamine D1 receptors. ... This differential modulation of PFC-dependent processes across dose appears to be associated with the differential involvement of noradrenergic α2 versus α1 receptors.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  19. ^ a b Haenisch, B.; Walstab, J.; Herberhold, S.; Bootz, F.; Tschaikin, M.; Ramseger, R.; Bönisch, H. (2009). "Alpha-adrenoceptor agonistic activity of oxymetazoline and xylometazoline". Fundamental & Clinical Pharmacology. 24 (6): 729–739. doi:10.1111/j.1472-8206.2009.00805.x. PMID 20030735. S2CID 25064699.
  20. ^ Young, R; CNS Drug Rev. (2007); et al. (2007). "TDIQ (5,6,7,8-tetrahydro-1,3-dioxolo [4,5-g]isoquinoline): discovery, pharmacological effects, and therapeutic potential". CNS Drug Reviews. 13 (4): 405–22. doi:10.1111/j.1527-3458.2007.00022.x. PMC 6494129. PMID 18078426.
  21. ^ Millan MJ, Cussac D, Milligan G, et al. (June 2001). "Antiparkinsonian agent piribedil displays antagonist properties at native, rat, and cloned, human alpha(2)-adrenoceptors: cellular and functional characterization". The Journal of Pharmacology and Experimental Therapeutics. 297 (3): 876–87. PMID 11356907.
  22. ^ Gobert A, Di Cara B, Cistarelli L, Millan MJ (April 2003). "Piribedil enhances frontocortical and hippocampal release of acetylcholine in freely moving rats by blockade of alpha 2A-adrenoceptors: a dialysis comparison to talipexole and quinelorane in the absence of acetylcholinesterase inhibitors". The Journal of Pharmacology and Experimental Therapeutics. 305 (1): 338–46. doi:10.1124/jpet.102.046383. PMID 12649387. S2CID 29234876.
  23. ^ Roth, BL; Driscol, J (12 January 2011). . Psychoactive Drug Screening Program (PDSP). University of North Carolina at Chapel Hill and the United States National Institute of Mental Health. Archived from the original on 8 November 2013. Retrieved 27 November 2013.
  24. ^ "Medscape Multispecialty – Home page". WebMD. Retrieved 27 November 2013.[full citation needed]
  25. ^ "Therapeutic Goods Administration – Home page". Department of Health (Australia). Retrieved 27 November 2013.[full citation needed]
  26. ^ "Daily Med – Home page". U.S. National Library of Medicine. Retrieved 27 November 2013.[full citation needed]
  27. ^ National Institute of Neurological Disorders and Stroke (2002). "Methylphenidate and Clonidine Help Children With ADHD and Tics".
  28. ^ "Clonidine Oral Uses". Web MD.
  29. ^ "EPAR summary for the public: Dexdomitor" (PDF). www.ema.europa.eu/ema/. European Medicines Agency. Retrieved July 22, 2017.
  30. ^ Crassous PA, Cardinaletti C, Carrieri A, Bruni B, Di Vaira M, Gentili F, Ghelfi F, Giannella M, Paris H, Piergentili A, Quaglia W, Schaak S, Vesprini C, Pigini M (August 2007). "Alpha2-adrenoreceptors profile modulation. 3.1 (R)-(+)-m-nitrobiphenyline, a new efficient and alpha2C-subtype selective agonist". Journal of Medicinal Chemistry. 50 (16): 3964–8. doi:10.1021/jm061487a. PMID 17630725.
  31. ^ Del Bello, Fabio; Mattioli, Laura; Ghelfi, Francesca; Giannella, Mario; Piergentili, Alessandro; Quaglia, Wilma; Cardinaletti, Claudia; Perfumi, Marina; Thomas, Russell J.; Zanelli, Ugo; Marchioro, Carla; Dal Cin, Michele; Pigini, Maria (11 November 2010). "Fruitful Adrenergic α2C-Agonism/α2A-Antagonism Combination to Prevent and Contrast Morphine Tolerance and Dependence". Journal of Medicinal Chemistry. 53 (21): 7825–7835. doi:10.1021/jm100977d. PMID 20925410.
  32. ^ . Archived from the original on 2007-08-24. Retrieved 2007-12-26.

External links

  • "Adrenoceptors". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology.

January 22, 2023
alpha, adrenergic, receptor, also, adrenergic, receptor, alpha, adrenergic, receptor, adrenoceptor, protein, coupled, receptor, gpcr, associated, with, heterotrimeric, protein, consists, three, highly, homologous, subtypes, including, α2a, α2b, α2c, adrenergic. See also Adrenergic receptor The alpha 2 a2 adrenergic receptor or adrenoceptor is a G protein coupled receptor GPCR associated with the Gi heterotrimeric G protein It consists of three highly homologous subtypes including a2A a2B and a2C adrenergic Some species other than humans express a fourth a2D adrenergic receptor as well 1 Catecholamines like norepinephrine noradrenaline and epinephrine adrenaline signal through the a2 adrenergic receptor in the central and peripheral nervous systems Contents 1 Cellular localization 2 Effects 2 1 General 2 2 Individual 3 Signaling cascade 3 1 Agonists 3 2 Antagonists 4 See also 5 References 6 External linksCellular localization EditThe a2A adrenergic receptor is localised in the following central nervous system CNS structures 2 Brainstem especially the locus coeruleus Midbrain Hypothalamus Hippocampus Spinal cord Cerebral cortex Cerebellum SeptumWhereas the a2B adrenergic receptor is localised in the following CNS structures 2 Olfactory system Thalamus Pyramidal layer of the hippocampus Cerebellar Purkinje layerand the a2C adrenergic receptor is localised in the CNS structures 2 Midbrain Thalamus Amygdala Dorsal root ganglia Olfactory system Hippocampus Cerebral cortex Basal ganglia Substantia nigra Ventral tegmentumEffects EditThe a2 adrenergic receptor is classically located on vascular prejunctional terminals where it inhibits the release of norepinephrine noradrenaline in a form of negative feedback 3 It is also located on the vascular smooth muscle cells of certain blood vessels such as those found in skin arterioles or on veins where it sits alongside the more plentiful a1 adrenergic receptor 3 The a2 adrenergic receptor binds both norepinephrine released by sympathetic postganglionic fibers and epinephrine adrenaline released by the adrenal medulla binding norepinephrine with slightly higher affinity 4 It has several general functions in common with the a1 adrenergic receptor but also has specific effects of its own Agonists activators of the a2 adrenergic receptor are frequently used in anaesthesia where they affect sedation muscle relaxation and analgesia through effects on the central nervous system CNS 5 General Edit Common effects include Suppression of release of norepinephrine noradrenaline by negative feedback 3 Transient hypertension increase in blood pressure followed by a sustained hypotension decrease in blood pressure 5 Vasoconstriction of certain arteries 6 Vasoconstriction of arteries to heart coronary artery 7 however the extent of this effect may be limited and may be negated by the vasodilatory effect from b2 receptors 8 Constriction of some vascular smooth muscle 9 Venoconstriction of veins 10 Decrease motility of smooth muscle in gastrointestinal tract 11 Inhibition of lipolysis 9 Facilitation of the cognitive functions associated with the prefrontal cortex PFC working memory attention executive functioning etc 12 Sedation 12 AnalgesiaIndividual Edit Individual actions of the a2 receptor include Mediates synaptic transmission in pre and postsynaptic nerve terminals Decrease release of acetylcholine 13 Decrease release of norepinephrine 13 Inhibit norepinephrine system in brain Inhibition 14 of lipolysis in adipose tissue 15 Inhibition of insulin release in pancreas 15 Induction of glucagon release from pancreas platelet aggregation Contraction of sphincters of the gastrointestinal tract Decreased secretion from salivary gland 5 Relax gastrointestinal tract presynaptic effect Decreased aqueous humor fluid production from the ciliary bodySignaling cascade EditThe a subunit of an inhibitory G protein Gi dissociates from the G protein 16 and associates with adenylyl cyclase This causes the inactivation of adenylyl cyclase resulting in a decrease of cAMP produced from ATP which leads to a decrease of intracellular cAMP PKA is not able to be activated by cAMP so proteins such as phosphorylase kinase cannot be phosphorylated by PKA In particular phosphorylase kinase is responsible for the phosphorylation and activation of glycogen phosphorylase an enzyme necessary for glycogen breakdown Thus in this pathway the downstream effect of adenylyl cyclase inactivation is decreased breakdown of glycogen The relaxation of gastrointestinal tract motility is by presynaptic inhibition 13 where transmitters inhibit further release by homotropic effects Agonists 4 NEMD 7 Me marsanidine also I1 agonist Agmatine also I agonist NMDA 5 HT3 nicotinic antagonist and NOS inhibitor Apraclonidine Brimonidine Cannabigerol also acts as a moderate affinity 5 HT1A receptor antagonist and low affinity CB1 receptor antagonist Clonidine also I1 agonist Detomidine Dexmedetomidine Fadolmidine Guanabenz Guanfacine Lofexidine Marsanidine Medetomidine Methamphetamine 17 Methylphenidate 18 Mivazerol Rilmenidine also I agonist Romifidine Talipexole also dopamine agonist Tiamenidine Tizanidine Tolonidine Xylazine Xylometazoline 19 Partial agonistsOxymetazoline also a1 agonist 19 TDIQ 20 Antagonists1 PP active metabolite of buspirone and gepirone Aripiprazole Asenapine Atipamezole Cirazoline Clozapine Efaroxan Idazoxan Lurasidone Melperone Mianserin Mirtazapine Napitane Olanzapine Paliperidone also primary active metabolite of Risperidone Phenoxybenzamine Phentolamine Piribedil 21 22 Rauwolscine Risperidone Rotigotine a2B antagonist non selective Quetiapine Norquetiapine primary active metabolite of Quetiapine Setiptiline Tolazoline Yohimbine Ziprasidone Zotepine discontinued Binding affinity Ki in nM and clinical data on a number of alpha 2 ligands 23 24 25 26 Drug a1A a1B a1D a2A a2B a2C Indication s Route of Administration Bioavailability Elimination half life Metabolising enzymes Protein bindingAgonistsClonidine 316 23 316 23 125 89 42 92 106 31 233 1 Hypertension ADHD analgesia sedation Oral epidural transdermal 75 85 IR 89 XR 12 16 h CYP2D6 20 40 Dexmedetomidine 199 53 316 23 79 23 6 13 18 46 37 72 Procedural and ICU sedation IV 100 6 minutes 94 Guanfacine 71 81 1200 2 2505 2 Hypertension ADHD Oral 80 100 IR 58 XR 17 h IR 18 h XR CYP3A4 70 Xylazine 5754 4 3467 4 gt 10000 Veterinary sedation Xylometazoline 15 14 1047 13 128 8 Nasal congestion Intranasal AntagonistsAsenapine 1 2 1 2 0 32 1 2 Schizophrenia bipolar disorder Sublingual 35 24 h CYP1A2 amp UGT1A4 95 Clozapine 1 62 7 37 25 6 Treatment resistant schizophrenia Oral 50 60 12 h CYP1A2 CYP3A4 CYP2D6 97 Mianserin 74 4 8 27 3 8 Depression Oral 20 21 61 h CYP3A4 95 Mirtazapine 500 20 18 Depression Oral 50 20 40 h CYP1A2 CYP2D6 CYP3A4 85 Agonists Edit Main article alpha adrenergic agonist Norepinephrine has higher affinity for the a2 receptor than has epinephrine and therefore relates less to the latter s functions 13 Nonselective a2 agonists include the antihypertensive drug clonidine 13 which can be used to lower blood pressure and to reduce hot flashes associated with menopause Clonidine has also been successfully used in indications that exceed what would be expected from a simple blood pressure lowering drug it has recently shown positive results in children with ADHD who have tics resulting from the treatment with a CNS stimulant drug such as Adderall XR or methylphenidate 27 clonidine also helps alleviate symptoms of opioid withdrawal 28 The hypotensive effect of clonidine was initially attributed through its agonist action on presynaptic a2 receptors which act as a down regulator on the amount of norepinephrine released in the synaptic cleft an example of autoreceptor However it is now known that clonidine binds to imidazoline receptors with a much greater affinity than a2 receptors which would account for its applications outside the field of hypertension alone Imidazoline receptors occur in the nucleus tractus solitarii and also the centrolateral medulla Clonidine is now thought to decrease blood pressure via this central mechanism Other nonselective agonists include dexmedetomidine lofexidine another antihypertensive TDIQ partial agonist tizanidine in spasms cramping and xylazine Xylazine has veterinary use In the European Union dexmedetomidine received a marketing authorization from the European Medicines Agency EMA on August 10 2012 under the brand name of Dexdor 29 It is indicated for sedation in the ICU for patients needing mechanical ventilation In non human species this is an immobilizing and anesthetic drug presumptively also mediated by a2 adrenergic receptors because it is reversed by yohimbine an a2 antagonist a2A selective agonists include guanfacine an antihypertensive and Brimonidine UK 14 304 R 3 nitrobiphenyline is an a2C selective agonist as well as being a weak antagonist at the a2A and a2B subtypes 30 31 Antagonists Edit Main article alpha blocker Nonselective a blockers include A 80426 atipamezole phenoxybenzamine efaroxan idazoxan 13 experimental 32 and SB 269 970 Yohimbine 13 is a relatively selective alpha 2 blocker that has been investigated as a treatment for erectile dysfunction Tetracyclic antidepressants mirtazapine and mianserin are also potent a antagonists with mirtazapine being more selective for a2 subtype 30 fold selective over a1 than mianserin 17 fold a2A selective blockers include BRL 44408 and RX 821 002 a2B selective blockers include ARC 239 and imiloxan a2C selective blockers include JP 1302 and spiroxatrine the latter also being a serotonin 5 HT1A antagonist See also EditAdrenergic receptorReferences Edit Ruuskanen JO Xhaard H Marjamaki A Salaneck E Salminen T Yan YL Postlethwait JH Johnson MS Larhammar D Scheinin M January 2004 Identification of duplicated fourth alpha2 adrenergic receptor subtype by cloning and mapping of five receptor genes in zebrafish Molecular Biology and Evolution 21 1 14 28 doi 10 1093 molbev msg224 PMID 12949138 a b c Saunders C Limbird LE November 1999 Localization and trafficking of alpha2 adrenergic receptor subtypes in cells and tissues Pharmacology amp Therapeutics 84 2 193 205 doi 10 1016 S0163 7258 99 00032 7 PMID 10596906 a b c Cardiovascular Physiology 3rd Edition Arnold Publishers Levick J R Chapter 14 1 Sympathetic vasoconstrictor nerves Boron Walter F 2012 Medical Physiology A Cellular and Molecular Approach p 360 a b c Khan ZP Ferguson CN Jones RM February 1999 alpha 2 and imidazoline receptor agonists Their pharmacology and therapeutic role Anaesthesia 54 2 146 65 doi 10 1046 j 1365 2044 1999 00659 x PMID 10215710 Goodman Gilman Alfred Goodman amp Gilman s The Pharmacological Basis of Therapeutics Tenth Edition McGraw Hill 2001 Page 140 Woodman OL Vatner SF 1987 Coronary vasoconstriction mediated by a1 and a2 adrenoceptors in conscious dogs Am J Physiol 253 2 Pt 2 H388 93 doi 10 1152 ajpheart 1987 253 2 H388 PMID 2887122 Sun D Huang A Mital S Kichuk M R Marboe C C Addonizio L J Michler R E Koller A Hintze T H Kaley G 2002 Norepinephrine elicits beta2 receptor mediated dilation of isolated human coronary arterioles Circulation 106 5 550 555 doi 10 1161 01 CIR 0000023896 70583 9F PMID 12147535 a b Basic amp Clinical Pharmacology 11th Edition McGrawHill LANGE Katzung Betram G Chapter 9 Adrenoceptor Agonists amp Sympathomimetic Drugs Elliott J 1997 Alpha adrenoceptors in equine digital veins evidence for the presence of both a1 and a2 receptors mediating vasoconstriction J Vet Pharmacol Ther 20 4 308 17 doi 10 1046 j 1365 2885 1997 00078 x PMID 9280371 Sagrada A Fargeas MJ Bueno L 1987 Involvement of a1 and a2 adrenoceptors in the postlaparotomy intestinal motor disturbances in the rat Gut 28 8 955 9 doi 10 1136 gut 28 8 955 PMC 1433140 PMID 2889649 a b Arnsten AFT 26 July 2007 Alpha 2 Agonists in the Treatment of ADHD Medscape Psychiatry WebMD Retrieved 13 November 2013 a b c d e f g Rang H P 2003 Pharmacology Edinburgh Churchill Livingstone ISBN 978 0 443 07145 4 Page 163 Wright EE Simpson ER 1981 Inhibition of the lipolytic action of beta adrenergic agonists in human adipocytes by alpha adrenergic agonists J Lipid Res 22 8 1265 70 doi 10 1016 S0022 2275 20 37319 3 PMID 6119348 a b Fitzpatrick David Purves Dale Augustine George 2004 Table 20 2 Neuroscience Third ed Sunderland Mass Sinauer ISBN 978 0 87893 725 7 Kou Qin Pooja R Sethi Nevin A Lambert August 2008 Abundance and stability of complexes containing inactive G protein coupled receptors and G proteins The FASEB Journal 22 8 2920 2927 doi 10 1096 fj 08 105775 PMC 2493464 PMID 18434433 Methamphetamine Targets DrugBank University of Alberta 8 February 2013 Retrieved 31 December 2013 Spencer RC Devilbiss DM Berridge CW June 2015 The Cognition Enhancing Effects of Psychostimulants Involve Direct Action in the Prefrontal Cortex Biol Psychiatry 77 11 940 950 doi 10 1016 j biopsych 2014 09 013 PMC 4377121 PMID 25499957 The procognitive actions of psychostimulants are only associated with low doses cognition enhancing effects of psychostimulants involve the preferential elevation of catecholamines in the PFC and the subsequent activation of norepinephrine a2 and dopamine D1 receptors This differential modulation of PFC dependent processes across dose appears to be associated with the differential involvement of noradrenergic a2 versus a1 receptors a href Template Cite journal html title Template Cite journal cite journal a CS1 maint multiple names authors list link a b Haenisch B Walstab J Herberhold S Bootz F Tschaikin M Ramseger R Bonisch H 2009 Alpha adrenoceptor agonistic activity of oxymetazoline and xylometazoline Fundamental amp Clinical Pharmacology 24 6 729 739 doi 10 1111 j 1472 8206 2009 00805 x PMID 20030735 S2CID 25064699 Young R CNS Drug Rev 2007 et al 2007 TDIQ 5 6 7 8 tetrahydro 1 3 dioxolo 4 5 g isoquinoline discovery pharmacological effects and therapeutic potential CNS Drug Reviews 13 4 405 22 doi 10 1111 j 1527 3458 2007 00022 x PMC 6494129 PMID 18078426 Millan MJ Cussac D Milligan G et al June 2001 Antiparkinsonian agent piribedil displays antagonist properties at native rat and cloned human alpha 2 adrenoceptors cellular and functional characterization The Journal of Pharmacology and Experimental Therapeutics 297 3 876 87 PMID 11356907 Gobert A Di Cara B Cistarelli L Millan MJ April 2003 Piribedil enhances frontocortical and hippocampal release of acetylcholine in freely moving rats by blockade of alpha 2A adrenoceptors a dialysis comparison to talipexole and quinelorane in the absence of acetylcholinesterase inhibitors The Journal of Pharmacology and Experimental Therapeutics 305 1 338 46 doi 10 1124 jpet 102 046383 PMID 12649387 S2CID 29234876 Roth BL Driscol J 12 January 2011 PDSP Ki Database Psychoactive Drug Screening Program PDSP University of North Carolina at Chapel Hill and the United States National Institute of Mental Health Archived from the original on 8 November 2013 Retrieved 27 November 2013 Medscape Multispecialty Home page WebMD Retrieved 27 November 2013 full citation needed Therapeutic Goods Administration Home page Department of Health Australia Retrieved 27 November 2013 full citation needed Daily Med Home page U S National Library of Medicine Retrieved 27 November 2013 full citation needed National Institute of Neurological Disorders and Stroke 2002 Methylphenidate and Clonidine Help Children With ADHD and Tics Clonidine Oral Uses Web MD EPAR summary for the public Dexdomitor PDF www ema europa eu ema European Medicines Agency Retrieved July 22 2017 Crassous PA Cardinaletti C Carrieri A Bruni B Di Vaira M Gentili F Ghelfi F Giannella M Paris H Piergentili A Quaglia W Schaak S Vesprini C Pigini M August 2007 Alpha2 adrenoreceptors profile modulation 3 1 R m nitrobiphenyline a new efficient and alpha2C subtype selective agonist Journal of Medicinal Chemistry 50 16 3964 8 doi 10 1021 jm061487a PMID 17630725 Del Bello Fabio Mattioli Laura Ghelfi Francesca Giannella Mario Piergentili Alessandro Quaglia Wilma Cardinaletti Claudia Perfumi Marina Thomas Russell J Zanelli Ugo Marchioro Carla Dal Cin Michele Pigini Maria 11 November 2010 Fruitful Adrenergic a2C Agonism a2A Antagonism Combination to Prevent and Contrast Morphine Tolerance and Dependence Journal of Medicinal Chemistry 53 21 7825 7835 doi 10 1021 jm100977d PMID 20925410 online medical dictionary org Archived from the original on 2007 08 24 Retrieved 2007 12 26 External links Edit Adrenoceptors IUPHAR Database of Receptors and Ion Channels International Union of Basic and Clinical Pharmacology Retrieved from https en wikipedia org w index php title Alpha 2 adrenergic receptor amp oldid 1108458439, wikipedia, wiki, book, books, library,

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