Anadrenergic agonist is adrug that stimulates a response from theadrenergic 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 andnorepinephrine areendogenous and broad-spectrum. More selective agonists are more useful in pharmacology.
Anadrenergic agent is adrug, or other substance, which has effects similar to, or the same as,epinephrine (adrenaline). Thus, it is a kind ofsympathomimetic agent. Alternatively, it may refer to something which is susceptible to epinephrine, or similar substances, such as a biologicalreceptor (specifically, theadrenergic receptors).
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 ofadenylate cyclase orphospholipase 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 activatephospholipase C (via Gq), increasing the activity ofprotein kinase C (PKC); α2 receptors inhibit adenylate cyclase (via Gi), decreasing the activity ofprotein 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]
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 andcatechol-o-methyl transferase. Respectively, these enzymes oxidise monoamines (including catecholamines) and methylate the hydroxyl 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]
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]
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]
These drugs act directly on one or more adrenergic receptors. According to receptor selectivity they are two types:
These are agents that increase neurotransmission in endogenous chemicals, namelyepinephrine andnorepinephrine. The most common mechanisms of action includes competitive and non-competitive reuptake inhibition and releasing agents. Examples include methylphenidate,atomoxetine, cocaine, and someamphetamine based stimulants such as4-hydroxyamphetamine.
