a treatment for glaucoma; the eyedrops reduce intraocular pressure by decreasing the production of aqueous humor and increasing its drainage through the uveoscleral pathway
(biochemistry) a drug that can combine with a receptor on a cell to produce a physiological reaction
a muscle that contracts while another relaxes; "when bending the elbow the biceps are the agonist"
someone involved in a contest or battle (as in an agon)
An adrenergic agonist is a drug that stimulates a response from the adrenergic receptors. The five main categories of adrenergic receptors are: α1, α2, β1, β2, and β3, although there are more subtypes, and agonists vary in specificity between these receptors, and may be classified respectively. However, there are also other mechanisms of adrenergic agonism. Epinephrine and norepinephrine are endogenous and broad-spectrum. More selective agonists are more useful in pharmacology.
An adrenergic agent is a drug, or other substance, which has effects similar to, or the same as, epinephrine (adrenaline). Thus, it is a kind of sympathomimetic agent. Alternatively, it may refer to something which is susceptible to epinephrine, or similar substances, such as a biological receptor (specifically, the adrenergic receptors).
Contents
1Receptors
2Uptake and storage
3Structure–activity relationship
4Mechanisms
4.1Direct action
4.2Indirect action
4.3Mixed action
5See also
6References
7External links
Receptors
Further information: Adrenergic receptor
Directly acting adrenergic agonists act on adrenergic receptors. All adrenergic receptors are G-protein coupled, activating signal transduction pathways. The G-protein receptor can affect the function of adenylate cyclase or phospholipase C, an agonist of the receptor will upregulate the effects on the downstream pathway (it will not necessarily upregulate the pathway itself).
The receptors are broadly grouped into α and β receptors. There are two subclasses of α-receptor, α1 and α2 which are further subdivided into α1A, α1B, α1D, α2A, α2B and α2C. The α2C receptor has been reclassed from α1C, due to its greater homology with the α2 class, giving rise to the somewhat confusing nomenclature. The β receptors are divided into β1, β2 and β3. The receptors are classed physiologically, though pharmacological selectivity for receptor subtypes exists and is important in the clinical application of adrenergic agonists (and, indeed, antagonists).
From an overall perspective, α1 receptors activate phospholipase C (via Gq), increasing the activity of protein kinase C (PKC); α2 receptors inhibit adenylate cyclase (via Gi), decreasing the activity of protein kinase A (PKA); β receptors activate adenylate cyclase (via Gs), thus increasing the activity of PKA. Agonists of each class of receptor elicit these downstream responses.[1]
Uptake and storage
Indirectly acting adrenergic agonists affect the uptake and storage mechanisms involved in adrenergic signalling.
Two uptake mechanisms exist for terminating the action of adrenergic catecholamines - uptake 1 and uptake 2. Uptake 1 occurs at the presynaptic nerve terminal to remove the neurotransmitter from the synapse. Uptake 2 occurs at postsynaptic and peripheral cells to prevent the neurotransmitter from diffusing laterally.
There is also enzymatic degradation of the catecholamines by two main enzymes - monoamine oxidase and catechol-o-methyl transferase. Respectively, these enzymes oxidise monoamines (including catecholamines) and methylate the hydroxal groups of the phenyl moiety of catecholamines. These enzymes can be targeted pharmacologically. Inhibitors of these enzymes act as indirect agonists of adrenergic receptors as they prolong the action of catecholamines at the receptors.[2]
Structure–activity relationship
In general, a primary or secondary aliphatic amine separated by 2 carbons from a substituted benzene ring is minimally required for high agonist activity.[3]
Mechanisms
A great number of drugs are available which can affect adrenergic receptors.. Other drugs affect the uptake and storage mechanisms of adrenergic catecholamines, prolonging their action. The following headings provide some useful examples to illustrate the various ways in which drugs can enhance the effects of adrenergic receptors.[4][5][6]
Direct action
These drugs act directly on one or more adrenergic receptors. According to receptor selectivity they are two types:
Non-selective: drugs act on one or more receptors; these are:
Adrenaline (almost all adrenergic receptors).
Noradrenaline (acts on α1, α2, β1).
Isoprenaline (acts on β1, β2, β3).
Dopamine (acts on α1, α2, β1, D1, D2).
Selective: drugs which act on a single receptor only; these are further classified into α selective & β selective.
DIRECT-ID: An automated method to identify and quantify conformational variations-application to β2 -adrenergic GPCR.
Lakkaraju SK1, Lemkul JA1, Huang J1, MacKerell AD Jr1.
Journal of computational chemistry.J Comput Chem.2016 Feb 5;37(4):416-25. doi: 10.1002/jcc.24231. Epub 2015 Nov 12.
The conformational dynamics of a macromolecule can be modulated by a number of factors, including changes in environment, ligand binding, and interactions with other macromolecules, among others. We present a method that quantifies the differences in macromolecular conformational dynamics and automa
Clonidine complexation with hydroxypropyl-beta-cyclodextrin: From physico-chemical characterization to in vivo adjuvant effect in local anesthesia.
Braga MA1, Martini MF2, Pickholz M2, Yokaichiya F3, Franco MK4, Cabeça LF5, Guilherme VA1, Silva CM1, Limia CE1, de Paula E6.
Journal of pharmaceutical and biomedical analysis.J Pharm Biomed Anal.2016 Feb 5;119:27-36. doi: 10.1016/j.jpba.2015.11.015. Epub 2015 Nov 18.
Clonidine (CND), an alpha-2-adrenergic agonist, is used as an adjuvant with local anesthetics. In this work, we describe the preparation and characterization of an inclusion complex of clonidine in hydroxypropyl-beta-cyclodextrin (HP-β-CD), as revealed by experimental (UV-vis absorption, SEM, X-ray
Dexmedetomidine added to an opioid-based analgesic regimen for the prevention of postoperative nausea and vomiting in highly susceptible patients: A randomised controlled trial.
Song Y1, Shim JK, Song JW, Kim EK, Kwak YL.
European journal of anaesthesiology.Eur J Anaesthesiol.2016 Feb;33(2):75-83. doi: 10.1097/EJA.0000000000000327.
BACKGROUND: Dexmedetomidine, an α2 adrenergic receptor agonist, has analgesic, sedative and sympatholytic properties, with a lack of respiratory depression. It is licensed only for intensive care sedation.OBJECTIVE: The objective of this study is to investigate whether intravenous (i.v.) patient-co
adrenergic agonist A family of agents which have adrenaline-like effects, acting directly or indirectly on any of the five G-protein-coupled adrenergic receptors: apha1, alpha2, beta1, beta2, beta3. Actions of adrenergic agonists alpha1 ...
