The adrenergic receptors or adrenoceptors are a class of G protein-coupled receptors that are targets of many catecholamines like norepinephrine (noradrenaline) and epinephrine (adrenaline) produced by the body, but also many medications like beta blockers, β2 agonists and α2 agonists, which are used to treat high blood pressure and asthma, for example.
Long-acting β adrenoceptor agonists are usually prescribed for moderate-to-severe persistent asthma patients or patients with chronic obstructive pulmonary disease (COPD). They are designed to reduce the need for shorter-acting β2 agonists such as salbutamol (albuterol), as they have a duration of action of approximately 12 hours in comparison with the 4-to-6-hour duration of salbutamol, making them candidates for sparing high doses of corticosteroids or treating nocturnal asthma and providing symptomatic improvement in patients with COPD. With the exception of formoterol, long-acting β2 agonists are not recommended for the treatment of acute asthma exacerbations because of their slower onset of action compared to salbutamol. Their long duration of action is due to the addition of a long, lipophilic side-chain that binds to an exosite on adrenergic receptors. This allows the active portion of the molecule to continuously bind and unbind at β2 receptors in the smooth muscle in the lungs.
Bisoprolol, marketed under the tradename Zebeta among others, is a medication most commonly used for heart diseases. This specifically includes high blood pressure, chest pain from not enough blood flow to the heart, and heart failure. It is taken by mouth.
Xamoterol is a cardiac stimulant. It works by binding to the β1 adrenergic receptor. It is a 3rd generation adrenergic β receptor partial agonist. It provides cardiac stimulation at rest but it acts as a blocker during exercise.
The beta-3 adrenergic receptor, also known as ADRB3, is a beta-adrenergic receptor, and also denotes the human gene encoding it.
Amibegron (SR-58,611A) was a drug developed by Sanofi-Aventis which acts as a selective agonist for the β3 adrenergic receptor. It is the first orally active β3 agonist developed that is capable of entering the central nervous system, and has antidepressant and anxiolytic effects.
Beta adrenergic agonists or beta agonists are medications that relax muscles of the airways, which widen the airways and result in easier breathing. They are a class of sympathomimetic agents which act upon the beta adrenoceptors. In general, pure beta-adrenergic agonists have the opposite function of beta blockers. Beta adrenoreceptor agonist ligands mimic the action of epinephrine and norepinephrine signaling in the heart, lungs, and smooth muscle tissue, with epinephrine expressing the highest affinity. The activation of β1, β2 and β3 activates the enzyme, adenylate cyclase. This, in turn, leads to the activation of the secondary messenger cyclic adenosine monophosphate (cAMP), cAMP then activates protein kinase A (PKA) which phosphorylates target proteins, ultimately inducing smooth muscle relaxation and contraction of the cardiac tissue.
Urapidil is a sympatholytic antihypertensive drug. It acts as an α1-adrenoceptor antagonist and as an 5-HT1A receptor agonist. Although an initial report suggested that urapidil was also an α2-adrenoceptor agonist, this was not substantiated in later studies that demonstrated it was devoid of agonist actions in the dog saphenous vein and the guinea-pig ileum. Unlike some other α1-adrenoceptor antagonists, urapidil does not elicit reflex tachycardia, and this may be related to its weak β1-adrenoceptor antagonist activity, as well as its effect on cardiac vagal drive. Urapidil is currently not approved by the U.S. Food and Drug Administration, but it is available in Europe.
Tretoquinol is a beta-adrenergic agonist.
Cyanopindolol is a drug related to pindolol which acts as both a β1 adrenoceptor antagonist and a 5-HT1A receptor antagonist. Its radiolabelled derivative iodocyanopindolol has been widely used in mapping the distribution of beta adrenoreceptors in the body.
Iodocyanopindolol (INN) is a drug related to pindolol which acts as both a β1 adrenoreceptor antagonist and a 5-HT1A receptor antagonist. Its 125I radiolabelled derivative has been widely used in mapping the distribution of beta adrenoreceptors in the body.
ICI-118,551 is a selective β2 adrenergic receptor (adrenoreceptor) antagonist or beta blocker. ICI binds to the β2 subtype with at least 100 times greater affinity than β1 or β3, the two other known subtypes of the beta adrenoceptor. The compound was developed by Imperial Chemical Industries, which was acquired by AkzoNobel in 2008.
SR 59230A is a selective antagonist of the beta-3 adrenergic receptor, but was subsequently shown to also act at α1 adrenoceptors at high doses. It has been shown to block the hyperthermia produced by MDMA in animal studies.
Adimolol (MEN-935) is antihypertensive agent which acts as a non-selective α1-, α2-, and β-adrenergic receptor antagonist.
Fluparoxan (GR50360A) (+/-)-(trans)-5-fluoro-2,3,3a,9a-tetrahydro-1H-[1,4]benzodioxino[2,3-c]pyrrole hydrochloride hemihydrate is a potent α2-adrenergic receptor antagonist with excellent α2/α1 selectivity, and is the only well-studied a2 antagonist in its structural family which does not antagonize any variant of the imidazoline receptor. It was shown to possess central α2-adrenoceptor antagonist activity after oral doses in man and was patented as an antidepressant by Glaxo in the early 1980s, but its development was discontinued when the compound failed to show a clear clinical advantage over existing therapies.
Raymond Perry Ahlquist was an American pharmacist and pharmacologist. He published seminal work in 1948 that divided adrenoceptors into α- and β-adrenoceptor subtypes. This discovery explained the activity of several existing drugs and also laid the ground work for new drugs including the widely prescribed beta blockers.
β2-adrenoceptor agonists is a group of drugs that act selectively on β2-receptors in the lungs causing bronchodilation. β2-agonists are used to treat asthma and COPD, diseases that cause obstruction in the airways. The first β2-agonist isoproterenol, an unselective agonist which was discovered in the 1940s. The aim of the drug development through the years has been to minimise side effects, achieve selectivity and longer duration of action. The mechanism of action is well understood and has facilitated the development. The structure of the binding site and the nature of the binding is also well known, as is the structure activity relationship.
PF-610355 is an inhalable ultra-long-acting β2 adrenoreceptor agonist (ultra-LABA) that was investigated as a treatment of asthma and COPD by Pfizer. It utilizes a sulfonamide agonist headgroup, that confers high levels of intrinsic crystallinity that could relate to the acidic sulfonamide motif supporting a zwitterionic form in the solid state. Optimization of pharmacokinetic properties minimized systemic exposure following inhalation and reduced systemically-mediated adverse events. Its in vivo duration on action confirmed its potential for once-daily use in humans.
A Beta-2 adrenergic antagonist is an adrenergic antagonist which blocks the beta-2 adrenergic receptors of cells, with either high specificity like Butaxamine and ICI-118,551, or non-specifically like the non-selective betablocker Propranolol.
A Beta-3 adrenergic antagonist is an adrenergic antagonist which blocks the Beta-3 adrenergic receptors of cells, with either high specificity like L-748,328, L-748,337 and SR 59,230A or non-specifically like the non-selective betablocker Carvedilol.
