Alpha-adrenergic agonist

{{Infobox drug class

| Name = Alpha adrenergic agonist

| Image = Phenylephrine v2.svg

| ImageClass = skin-invert-image

| Alt = Phenylephrine

| Use = Decongestant, Hypotension, Bradycardia, Hypothermia etc.

| Caption = Skeletal structor formula of phenylephrine, a common nasal decongestant

| Biological_target = Alpha adrenergic receptors of the α subtype

| ATC_prefix = N07

| MeshID = D000316

}}

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

Image:Norepinephrine.svg (noradrenaline)]]

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).

=α<sub>1</sub> agonist=

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

Adrenoswitch-1 (photoswitchable partial α₁ agonist and light-controlled mydriatic){{cite journal | vauthors = Prischich D, Gomila AM, Milla-Navarro S, Sangüesa G, Diez-Alarcia R, Preda B, Matera C, Batlle M, Ramírez L, Giralt E, Hernando J, Guasch E, Meana JJ, de la Villa P, Gorostiza P | title = Adrenergic Modulation With Photochromic Ligands | journal = Angewandte Chemie | volume = 60 | issue = 7 | pages = 3625–3631 | date = February 2021 | pmid = 33103317 | doi = 10.1002/anie.202010553 | hdl-access = free | hdl = 2434/778579 }}
Methoxamine
Midodrine
Metaraminol
Phenylephrine{{cite journal | vauthors = Declerck I, Himpens B, Droogmans G, Casteels R | title = The alpha 1-agonist phenylephrine inhibits voltage-gated Ca2(+)-channels in vascular smooth muscle cells of rabbit ear artery | journal = Pflügers Archiv | volume = 417 | issue = 1 | pages = 117–119 | date = September 1990 | pmid = 1963492 | doi = 10.1007/BF00370780 | s2cid = 8074029 }}
Amidephrine{{cite journal | vauthors = MacLean MR, Thomson M, Hiley CR | title = Pressor effects of the alpha 2-adrenoceptor agonist B-HT 933 in anaesthetized and haemorrhagic rats: comparison with the haemodynamic effects of amidephrine | journal = British Journal of Pharmacology | volume = 97 | issue = 2 | pages = 419–432 | date = June 1989 | pmid = 2569342 | pmc = 1854522 | doi = 10.1111/j.1476-5381.1989.tb11969.x }}
[https://pubchem.ncbi.nlm.nih.gov/compound/128503 Sdz-nvi-085] [104195-17-7].

=α<sub>2</sub> 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:

Brimonidine
Clonidine (mixed alpha2-adrenergic and imidazoline-I1 receptor agonist)
Dexmedetomidine
Fadolmidine
Guanfacine,{{cite journal | vauthors = Sagvolden T | title = The alpha-2A adrenoceptor agonist guanfacine improves sustained attention and reduces overactivity and impulsiveness in an animal model of Attention-Deficit/Hyperactivity Disorder (ADHD) | journal = Behavioral and Brain Functions | volume = 2 | pages = 41 | date = December 2006 | pmid = 17173664 | pmc = 1764416 | doi = 10.1186/1744-9081-2-41 | doi-access = free }} (preference for alpha2A-subtype of adrenoceptor)
Guanabenz (most selective agonist for alpha2-adrenergic as opposed to imidazoline-I1)
Guanoxabenz (metabolite of guanabenz)
Xylazine (not approved for human use){{cite journal | vauthors = Atalik KE, Sahin AS, Doğan N | title = Interactions between phenylephrine, clonidine and xylazine in rat and rabbit aortas | journal = Methods and Findings in Experimental and Clinical Pharmacology | volume = 22 | issue = 3 | pages = 145–147 | date = April 2000 | pmid = 10893695 | doi = 10.1358/mf.2000.22.3.796096 | s2cid = 8218673 }}
Tizanidine
Methyldopa
Methylnorepinephrine
Norepinephrine{{cite journal | vauthors = Lemke KA | title = Perioperative use of selective alpha-2 agonists and antagonists in small animals | journal = The Canadian Veterinary Journal | volume = 45 | issue = 6 | pages = 475–480 | date = June 2004 | pmid = 15283516 | pmc = 548630 }}
(R)-3-nitrobiphenyline, an α_2C selective agonist as well as a weak antagonist at the α{{sub|2A}} and α{{sub|2B}} subtypes.{{cite journal | vauthors = 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 | title = Alpha2-adrenoreceptors profile modulation. 3.1 (R)-(+)-m-nitrobiphenyline, a new efficient and alpha2C-subtype selective agonist | journal = Journal of Medicinal Chemistry | volume = 50 | issue = 16 | pages = 3964–3968 | date = August 2007 | pmid = 17630725 | doi = 10.1021/jm061487a }}{{cite journal | vauthors = Del Bello F, Mattioli L, Ghelfi F, Giannella M, Piergentili A, Quaglia W, Cardinaletti C, Perfumi M, Thomas RJ, Zanelli U, Marchioro C, Dal Cin M, Pigini M | title = Fruitful adrenergic α(2C)-agonism/α(2A)-antagonism combination to prevent and contrast morphine tolerance and dependence | journal = Journal of Medicinal Chemistry | volume = 53 | issue = 21 | pages = 7825–7835 | date = November 2010 | pmid = 20925410 | doi = 10.1021/jm100977d }}
Amitraz{{cite journal | vauthors = Hsu WH, Lu ZX | title = Amitraz-induced delay of gastrointestinal transit in mice: Mediated by α2-adrenergic receptors. | journal = Drug Development Research | date = 1984 | volume = 4 | issue = 6 | pages = 655–660 | doi = 10.1002/ddr.430040608 }}
Detomidine{{Cite web |title=Detomidine {{!}} α2-adrenergic Agonist {{!}} MedChemExpress |url=https://www.medchemexpress.com/detomidine.html?srsltid=AfmBOop2_l6_W7WPv9Ky9jWhDf64HSbIcSOZOCi8tA0mUmiLHrM2bPAB |access-date=2024-11-29 |website=MedchemExpress.com}}
Lofexidine, an α_2A adrenergic receptor agonist.{{cite web|url=https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm607884.htm|title=Press Announcements - FDA approves the first non-opioid treatment for management of opioid withdrawal symptoms in adults|website=www.fda.gov|language=en|access-date=18 May 2018}}
Medetomidine, an α2 adrenergic agonist.{{cite journal | vauthors = Sinclair MD | title = A review of the physiological effects of alpha2-agonists related to the clinical use of medetomidine in small animal practice | journal = The Canadian Veterinary Journal | volume = 44 | issue = 11 | pages = 885–897 | date = November 2003 | pmid = 14664351 | pmc = 385445 }}

= Nonspecific agonist =

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

Xylometazoline{{cite journal | vauthors = Haenisch B, Walstab J, Herberhold S, Bootz F, Tschaikin M, Ramseger R, Bönisch H | title = Alpha-adrenoceptor agonistic activity of oxymetazoline and xylometazoline | journal = Fundamental & Clinical Pharmacology | volume = 24 | issue = 6 | pages = 729–739 | date = December 2010 | pmid = 20030735 | doi = 10.1111/j.1472-8206.2009.00805.x | s2cid = 25064699 }}
Oxymetazoline{{cite book | vauthors = Westfall TC, Westfall DP | chapter = Chapter 6. Neurotransmission: The Autonomic and Somatic Motor Nervous Systems | veditors = Brunton LL, Lazo JS, Parker KL | title = Goodman & Gilman's The Pharmacological Basis of Therapeutics | edition = 11th | url = http://www.accessmedicine.com/content.aspx?aID=954433 |access-date=2015-01-24 |url-status=dead |archive-url=https://web.archive.org/web/20110930100924/http://www.accessmedicine.com/content.aspx?aID=954433 |archive-date=2011-09-30 }}
Apraclonidine{{Citation needed|date=May 2019}}
Cirazoline{{cite journal | vauthors = Horie K, Obika K, Foglar R, Tsujimoto G | title = Selectivity of the imidazoline alpha-adrenoceptor agonists (oxymetazoline and cirazoline) for human cloned alpha 1-adrenoceptor subtypes | journal = British Journal of Pharmacology | volume = 116 | issue = 1 | pages = 1611–1618 | date = September 1995 | pmid = 8564227 | pmc = 1908909 | doi = 10.1111/j.1476-5381.1995.tb16381.x }}{{cite journal | vauthors = Ruffolo RR, Waddell JE | title = Receptor interactions of imidazolines. IX. Cirazoline is an alpha-1 adrenergic agonist and an alpha-2 adrenergic antagonist | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 222 | issue = 1 | pages = 29–36 | date = July 1982 | doi = 10.1016/S0022-3565(25)33148-4 | pmid = 6123592 }}
Epinephrine{{Cite book|title=Illustrated Pharmacology Memory Cards: PharMnemonics| vauthors = Shen H |publisher=Minireview|year=2008|isbn=978-1-59541-101-3|pages=4}}

=Undetermined/unsorted=

The following agents are also listed as agonists by MeSH.{{MeshPharmaList|82000316}}

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.{{cite journal | vauthors = Lewis SR, Nicholson A, Smith AF, Alderson P | title = Alpha-2 adrenergic agonists for the prevention of shivering following general anaesthesia | journal = The Cochrane Database of Systematic Reviews | volume = 2015 | issue = 8 | pages = CD011107 | date = August 2015 | pmid = 26256531 | pmc = 9221859 | doi = 10.1002/14651858.cd011107.pub2 }}

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.{{cite journal | vauthors = Duncan D, Sankar A, Beattie WS, Wijeysundera DN | title = Alpha-2 adrenergic agonists for the prevention of cardiac complications among adults undergoing surgery | journal = The Cochrane Database of Systematic Reviews | volume = 3 | issue = 3 | pages = CD004126 | date = March 2018 | pmid = 29509957 | pmc = 6494272 | doi = 10.1002/14651858.cd004126.pub3 }}

Alpha-2 adrenergic agonists are sometimes prescribed alone or in combination with stimulants to treat ADHD.{{cite book | vauthors = Coghill D |title=New Discoveries in the Behavioral Neuroscience of Attention-Deficit Hyperactivity Disorder |date=2022 |publisher=Springer International Publishing |isbn=978-3-031-11802-9 |pages=51–77 |chapter-url=https://link.springer.com/chapter/10.1007/7854_2022_331 |language=en |chapter=The Benefits and Limitations of Stimulants in Treating ADHD|series=Current Topics in Behavioral Neurosciences |volume=57 |doi=10.1007/7854_2022_331 |pmid=35503597 }}

References

External links

{{Commonscatinline|Alpha agonists}}
{{MeshName|Adrenergic+alpha-Agonists}}