Alpha-adrenergic agonist explained

Alpha adrenergic agonist
Use:Decongestant, Hypotension, Bradycardia, Hypothermia etc.
Biological Target:Alpha adrenergic receptors of the α subtype
Atc Prefix:N07

Alpha-adrenergic agonists are a class of sympathomimetic agents that selectively stimulates alpha adrenergic receptors. The alpha-adrenergic receptor has two subclasses α1 and α2. Alpha 2 receptors are associated with sympatholytic properties. Alpha-adrenergic agonists have the opposite function of alpha blockers. Alpha adrenoreceptor ligands mimic the action of epinephrine and norepinephrine signaling in the heart, smooth muscle and central nervous system, with norepinephrine being the highest affinity. The activation of α1 stimulates the membrane bound enzyme phospholipase C, and activation of α2 inhibits the enzyme adenylate cyclase. Inactivation of adenylate cyclase in turn leads to the inactivation of the secondary messenger cyclic adenosine monophosphate and induces smooth muscle and blood vessel constriction.

Classes

Although complete selectivity between receptor agonism is rarely achieved, some agents have partial selectivity. NB: the inclusion of a drug in each category just indicates the activity of the drug at that receptor, not necessarily the selectivity of the drug (unless otherwise noted).

α1 agonist

α1 agonist: stimulates phospholipase C activity. (vasoconstriction and mydriasis; used as vasopressors, nasal decongestants and during eye exams). Selected examples are:

α2 agonist

α2 agonist: inhibits adenylyl cyclase activity, reduces brainstem vasomotor center-mediated CNS activation; used as antihypertensive, sedative & treatment of opiate dependence and alcohol withdrawal symptoms). Selected examples are:

Nonspecific agonist

Nonspecific agonists act as agonists at both alpha-1 and alpha-2 receptors.

Undetermined/unsorted

The following agents are also listed as agonists by MeSH.

Clinical significance

Alpha-adrenergic agonists, more specifically the auto receptors of alpha 2 neurons, are used in the treatment of glaucoma by decreasing the production of aqueous fluid by the ciliary bodies of the eye and also by increasing uveoscleral outflow. Medications such as clonidine and dexmedetomidine target pre-synaptic auto receptors, therefore leading to an overall decrease in norepinephrine which clinically can cause effects such as sedation, analgesia, lowering of blood pressure and bradycardia. There is also low quality evidence that they can reduce shivering post operatively.[17]

The reduction of the stress response caused by alpha 2 agonists were theorised to be beneficial peri operatively by reducing cardiac complications, however this has shown not to be clinically effective as there was no reduction in cardiac events or mortality but there was an increased incidence of hypotension and bradycardia.[18]

Alpha-2 adrenergic agonists are sometimes prescribed alone or in combination with stimulants to treat ADHD.[19]

See also

Notes and References

  1. Prischich . Davia . Gomila . Alexandre M. J. . Milla‐Navarro . Santiago . Sangüesa . Gemma . Diez‐Alarcia . Rebeca . Preda . Beatrice . Matera . Carlo . Batlle . Montserrat . Ramírez . Laura . Giralt . Ernest . Hernando . Jordi . Guasch . Eduard . Meana . J. Javier . de la Villa . Pedro . Gorostiza . Pau . 2021-02-15 . Adrenergic Modulation With Photochromic Ligands . Angewandte Chemie International Edition . en . 60 . 7 . 3625–3631 . 10.1002/anie.202010553 . 1433-7851. 2434/778579 . free .
  2. Declerck I, Himpens B, Droogmans G, Casteels R . The alpha 1-agonist phenylephrine inhibits voltage-gated Ca2(+)-channels in vascular smooth muscle cells of rabbit ear artery . Pflügers Arch. . 417 . 1 . 117–9 . September 1990 . 1963492 . 10.1007/BF00370780. 8074029 .
  3. MacLean MR, Thomson M, Hiley CR. June 1989. Pressor effects of the alpha 2-adrenoceptor agonist B-HT 933 in anaesthetized and haemorrhagic rats: comparison with the haemodynamic effects of amidephrine. Br. J. Pharmacol.. 97. 2. 419–32. 10.1111/j.1476-5381.1989.tb11969.x. 1854522. 2569342.
  4. Sagvolden T . The alpha-2A adrenoceptor agonist guanfacine improves sustained attention and reduces overactivity and impulsiveness in an animal model of Attention-Deficit/Hyperactivity Disorder (ADHD) . Behav Brain Funct . 2 . 41 . 2006 . 17173664 . 1764416 . 10.1186/1744-9081-2-41 . free .
  5. Atalik KE, Sahin AS, Doğan N . Interactions between phenylephrine, clonidine and xylazine in rat and rabbit aortas . Methods Find Exp Clin Pharmacol . 22 . 3 . 145–7 . April 2000 . 10.1358/mf.2000.22.3.796096 . 10893695 . 8218673 .
  6. Lemke KA . Perioperative use of selective alpha-2 agonists and antagonists in small animals . Can. Vet. J. . 45 . 6 . 475–80 . 2004 . 15283516 . 548630.
  7. 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 . 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 . 17630725 . 10.1021/jm061487a . August 2007.
  8. 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. Fruitful Adrenergic α2C-Agonism/α2A-Antagonism Combination to Prevent and Contrast Morphine Tolerance and Dependence. Journal of Medicinal Chemistry. 11 November 2010. 53. 21. 7825–7835. 10.1021/jm100977d. 20925410.
  9. Hsu, W. H. and Lu, Z.-X. (1984). Amitraz' induced delay of gastrointestinal transit in mice: Mediated by α2 adrenergic receptors. Drug Development Research, Volume 4 (6), 655- 680.
  10. Web site: Press Announcements - FDA approves the first non-opioid treatment for management of opioid withdrawal symptoms in adults. www.fda.gov. en. 18 May 2018.
  11. Sinclair MD. November 2003. A review of the physiological effects of alpha2-agonists related to the clinical use of medetomidine in small animal practice. Can. Vet. J.. 44. 11. 885–97. 385445. 14664351.
  12. Haenisch . B. . Walstab . J. . Herberhold . S. . Bootz . F. . Tschaikin . M. . Ramseger . R. . Bönisch . H. . Alpha-adrenoceptor Agonistic Activity of Oxymetazoline and Xylometazoline . Fundamental & Clinical Pharmacology . 24 . 6 . 729–39 . 2009 . 20030735 . 10.1111/j.1472-8206.2009.00805.x. 25064699 .
  13. Westfall Thomas C, Westfall David P, "Chapter 6. Neurotransmission: The Autonomic and Somatic Motor Nervous Systems" (Chapter). Brunton LL, Lazo JS, Parker KL: Goodman & Gilman's The Pharmacological Basis of Therapeutics, 11e: Web site: AccessMedicine | Anatomy and General Functions of the Autonomic and Somatic Motor Nervous Systems . 2015-01-24 . dead . https://web.archive.org/web/20110930100924/http://www.accessmedicine.com/content.aspx?aID=954433 . 2011-09-30 . .
  14. Horie, K. Obika, K. Foglar, R. 1995. Selectivity of the imidazoline α-adrenoceptor agonists (oxymetazoline and cirazoline) for human cloned α1-adrenoceptor subtypes. British Journal of Pharmacology. 116. 1. 1611–8. 10.1111/j.1476-5381.1995.tb16381.x. 1908909. 8564227.
  15. Ruffolo, R. R. Jr.. Waddell, J. E.. 1982. Receptor interactions of imidazolines. IX. Cirazoline is an α1 adrenergic agonist and an α2 adrenergic antagonist. Journal of Pharmacology and Experimental Therapeutics. 222. 1. 29–36. 6123592.
  16. Book: Illustrated Pharmacology Memory Cards: PharMnemonics. Shen, Howard. Minireview. 2008. 978-1-59541-101-3. 4.
  17. Lewis. Sharon R. Nicholson. Amanda. Smith. Andrew F. Alderson. Phil. 2015-08-10. Alpha-2 adrenergic agonists for the prevention of shivering following general anaesthesia. Cochrane Database of Systematic Reviews. 2015 . 8. CD011107. 10.1002/14651858.cd011107.pub2. 26256531. 9221859 . 1465-1858.
  18. Duncan. Dallas. Sankar. Ashwin. Beattie. W Scott. Wijeysundera. Duminda N. 2018-03-06. Alpha-2 adrenergic agonists for the prevention of cardiac complications among adults undergoing surgery. Cochrane Database of Systematic Reviews. 2018. 3. CD004126. 10.1002/14651858.cd004126.pub3. 29509957. 1465-1858. 6494272.
  19. Book: Coghill . David . New Discoveries in the Behavioral Neuroscience of Attention-Deficit Hyperactivity Disorder . 2022 . Springer International Publishing . 978-3-031-11802-9 . 51–77 . https://link.springer.com/chapter/10.1007/7854_2022_331 . en . The Benefits and Limitations of Stimulants in Treating ADHD. Current Topics in Behavioral Neurosciences . 57 . 10.1007/7854_2022_331 . 35503597 .

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