Adrenergic
Encyclopedia
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 receptor
s).
Beta blocker
s block the action of epinephrine and norepinephrine in the body. Adrenergic drugs either stimulate a response (agonists) or inhibit a response (antagonists). The five categories of adrenergic receptors are: α1, α2, β1, β2, and β3, 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.
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.
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 two 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 targetted pharmacologically. Inhibitors of these enzymes act as indirect agonists of adrenergic receptors as they prolong the action of catecholamines at the receptors.
Medication
A pharmaceutical drug, also referred to as medicine, medication or medicament, can be loosely defined as any chemical substance intended for use in the medical diagnosis, cure, treatment, or prevention of disease.- Classification :...
, or other substance, which has effects similar to, or the same as, epinephrine
Epinephrine
Epinephrine is a hormone and a neurotransmitter. It increases heart rate, constricts blood vessels, dilates air passages and participates in the fight-or-flight response of the sympathetic nervous system. In chemical terms, adrenaline is one of a group of monoamines called the catecholamines...
(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
Receptor (biochemistry)
In biochemistry, a receptor is a molecule found on the surface of a cell, which receives specific chemical signals from neighbouring cells or the wider environment within an organism...
(specifically, the adrenergic receptor
Adrenergic receptor
The adrenergic receptors are a class of metabotropic G protein-coupled receptors that are targets of the catecholamines, especially noradrenaline and adrenaline ....
s).
Beta blocker
Beta blocker
Beta blockers or beta-adrenergic blocking agents, beta-adrenergic antagonists, beta-adrenoreceptor antagonists or beta antagonists, are a class of drugs used for various indications. They are particularly for the management of cardiac arrhythmias, cardioprotection after myocardial infarction ,...
s block the action of epinephrine and norepinephrine in the body. Adrenergic drugs either stimulate a response (agonists) or inhibit a response (antagonists). The five categories of adrenergic receptors are: α1, α2, β1, β2, and β3, and agonists vary in specificity between these receptors, and may be classified respectively. However, there are also other mechanisms of adrenergic agonism. Epinephrine
Epinephrine
Epinephrine is a hormone and a neurotransmitter. It increases heart rate, constricts blood vessels, dilates air passages and participates in the fight-or-flight response of the sympathetic nervous system. In chemical terms, adrenaline is one of a group of monoamines called the catecholamines...
and norepinephrine
Norepinephrine
Norepinephrine is the US name for noradrenaline , a catecholamine with multiple roles including as a hormone and a neurotransmitter...
are endogenous
Endogenous
Endogenous substances are those that originate from within an organism, tissue, or cell. Endogenous retroviruses are caused by ancient infections of germ cells in humans, mammals and other vertebrates...
and broad-spectrum. More selective agonists are more useful in pharmacology.
Receptors
For more info see adrenergic receptorAdrenergic receptor
The adrenergic receptors are a class of metabotropic G protein-coupled receptors that are targets of the catecholamines, especially noradrenaline and adrenaline ....
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
Adenylate cyclase
Adenylate cyclase is part of the G protein signalling cascade, which transmits chemical signals from outside the cell across the membrane to the inside of the cell ....
or phospholipase C
Phospholipase C
Phosphoinositide phospholipase C is a family of eukaryotic intracellular enzymes that play an important role in signal transduction processes. In general, this enzyme is denoted as Phospholipase C, although three other families of phospholipase C enzymes have been identified in bacteria and in...
, 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
Protein kinase C
Protein kinase C also known as PKC is a family of enzymes that are involved in controlling the function of other proteins through the phosphorylation of hydroxyl groups of serine and threonine amino acid residues on these proteins. PKC enzymes in turn are activated by signals such as increases in...
(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.
Uptake and Storage
Indirectly acting adrenergic agonists affect on 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 two 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
Monoamine oxidase
L-Monoamine oxidases are a family of enzymes that catalyze the oxidation of monoamines. They are found bound to the outer membrane of mitochondria in most cell types in the body. The enzyme was originally discovered by Mary Bernheim in the liver and was named tyramine oxidase...
and catechol-o-methyl transferase
Catechol-O-methyl transferase
Catechol-O-methyltransferase is one of several enzymes that degrade catecholamines such as dopamine, epinephrine, and norepinephrine. In humans, catechol-O-methyltransferase protein is encoded by the COMT gene...
. Respectively, these enzymes oxidise monoamines (including catecholamines) and methylate the hydroxal groups of the phenyl moiety of catecholamines. These enzymes can be targetted pharmacologically. Inhibitors of these enzymes act as indirect agonists of adrenergic receptors as they prolong the action of catecholamines at the receptors.
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.Mechanisms
A great number of drugs are available which can affect adrenergic receptors. Each drug has its own receptor specificity giving it a unique pharmacological effect. 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.Indirect action
- AmphetamineAmphetamineAmphetamine or amfetamine is a psychostimulant drug of the phenethylamine class which produces increased wakefulness and focus in association with decreased fatigue and appetite.Brand names of medications that contain, or metabolize into, amphetamine include Adderall, Dexedrine, Dextrostat,...
- CocaineCocaineCocaine is a crystalline tropane alkaloid that is obtained from the leaves of the coca plant. The name comes from "coca" in addition to the alkaloid suffix -ine, forming cocaine. It is a stimulant of the central nervous system, an appetite suppressant, and a topical anesthetic...
- MethylenedioxymethamphetamineMethylenedioxymethamphetamineMDMA is an entactogenic drug of the phenethylamine and amphetamine class of drugs. In popular culture, MDMA has become widely known as "ecstasy" , usually referring to its street pill form, although this term may also include the presence of possible adulterants...
(MDMA) - TyramineTyramineTyramine is a naturally occurring monoamine compound and trace amine derived from the amino acid tyrosine. Tyramine acts as a catecholamine releasing agent...