Alpha-adrenergicagonists are a class ofsympathomimetic agents that selectively stimulates alphaadrenergic receptors. The alpha-adrenergic receptor has two subclasses α1 and α2. Alpha 2 receptors are associated withsympatholytic properties. Alpha-adrenergic agonists have the opposite function ofalpha blockers. Alpha adrenoreceptor ligands mimic the action ofepinephrine andnorepinephrine signaling in the heart, smooth muscle and central nervous system, with norepinephrine being the highest affinity. The activation of α1 stimulates the membrane bound enzymephospholipase C, and activation of α2 inhibits the enzymeadenylate cyclase. Inactivation of adenylate cyclase in turn leads to the inactivation of the secondary messengercyclic adenosine monophosphate and induces smooth muscle and blood vessel constriction.
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: stimulatesphospholipase 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)[1]
Alpha-adrenergic agonists, more specifically the auto receptors of alpha 2 neurons, are used in the treatment ofglaucoma by decreasing the production of aqueous fluid by the ciliary bodies of the eye and also by increasing uveoscleral outflow. Medications such asclonidine anddexmedetomidine 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.[19]
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.[20]
Alpha-2 adrenergic agonists are sometimes prescribed alone or in combination with stimulants to treat ADHD.[21]
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^Del Bello F, Mattioli L, Ghelfi F, Giannella M, Piergentili A, Quaglia W, et al. (November 2010). "Fruitful adrenergic α(2C)-agonism/α(2A)-antagonism combination to prevent and contrast morphine tolerance and dependence".Journal of Medicinal Chemistry.53 (21):7825–7835.doi:10.1021/jm100977d.PMID20925410.
^Hsu WH, Lu ZX (1984). "Amitraz-induced delay of gastrointestinal transit in mice: Mediated by α2-adrenergic receptors".Drug Development Research.4 (6):655–660.doi:10.1002/ddr.430040608.
^Ruffolo RR, Waddell JE (July 1982). "Receptor interactions of imidazolines. IX. Cirazoline is an alpha-1 adrenergic agonist and an alpha-2 adrenergic antagonist".The Journal of Pharmacology and Experimental Therapeutics.222 (1):29–36.doi:10.1016/S0022-3565(25)33148-4.PMID6123592.
^Shen H (2008).Illustrated Pharmacology Memory Cards: PharMnemonics. Minireview. p. 4.ISBN978-1-59541-101-3.
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