The alpha-2 (α₂) adrenergic receptor (or adrenoceptor) is a

G protein-coupled receptor G protein-coupled receptors (GPCRs), also known as seven-(pass)-transmembrane domain receptors, 7TM receptors, heptahelical receptors, serpentine receptors, and G protein-linked receptors (GPLR), form a large group of evolutionarily related ...

(GPCR) associated with the G_i

heterotrimeric G-protein Heterotrimeric G protein, also sometimes referred to as the ''"large" G proteins'' (as opposed to the subclass of smaller, monomeric small GTPases) are membrane-associated G proteins that form a Heteromer, heterotrimeric complex. The biggest no ...

. It consists of three highly homologous subtypes, including α_2A-, α_2B-, and α_2C-adrenergic. Some species other than humans express a fourth α_2D-adrenergic receptor as well.

Catecholamine A catecholamine (; abbreviated CA), most typically a 3,4-dihydroxyphenethylamine, is a monoamine neurotransmitter, an organic compound that has a catechol (benzene with two hydroxyl side groups next to each other) and a side-chain amine. Cate ...

s like

norepinephrine Norepinephrine (NE), also called noradrenaline (NA) or noradrenalin, is an organic compound, organic chemical in the catecholamine family that functions in the brain and human body, body as a hormone, neurotransmitter and neuromodulator. The ...

(noradrenaline) and

epinephrine Adrenaline, also known as epinephrine, is a hormone and medication which is involved in regulating visceral functions (e.g., respiration). It appears as a white microcrystalline granule. Adrenaline is normally produced by the adrenal glands a ...

(adrenaline) signal through the α₂-adrenergic receptor in the central and

peripheral nervous system The peripheral nervous system (PNS) is one of two components that make up the nervous system of Bilateria, bilateral animals, with the other part being the central nervous system (CNS). The PNS consists of nerves and ganglia, which lie outside t ...

Cellular localization

The α_2A adrenergic receptor is localised in the following

central nervous system The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain, spinal cord and retina. The CNS is so named because the brain integrates the received information and coordinates and influences the activity o ...

(CNS) structures: *

Brainstem The brainstem (or brain stem) is the posterior stalk-like part of the brain that connects the cerebrum with the spinal cord. In the human brain the brainstem is composed of the midbrain, the pons, and the medulla oblongata. The midbrain is conti ...

(especially the

locus coeruleus The locus coeruleus () (LC), also spelled locus caeruleus or locus ceruleus, is a nucleus in the pons of the brainstem involved with physiological responses to stress and panic. It is a part of the reticular activating system in the reticular ...

as presynaptic & somatodendritic autoreceptor ) *

Midbrain The midbrain or mesencephalon is the uppermost portion of the brainstem connecting the diencephalon and cerebrum with the pons. It consists of the cerebral peduncles, tegmentum, and tectum. It is functionally associated with vision, hearing, mo ...

Hypothalamus The hypothalamus (: hypothalami; ) is a small part of the vertebrate brain that contains a number of nucleus (neuroanatomy), nuclei with a variety of functions. One of the most important functions is to link the nervous system to the endocrin ...

* Olfactory system *

Hippocampus The hippocampus (: hippocampi; via Latin from Ancient Greek, Greek , 'seahorse'), also hippocampus proper, is a major component of the brain of humans and many other vertebrates. In the human brain the hippocampus, the dentate gyrus, and the ...

Spinal cord The spinal cord is a long, thin, tubular structure made up of nervous tissue that extends from the medulla oblongata in the lower brainstem to the lumbar region of the vertebral column (backbone) of vertebrate animals. The center of the spinal c ...

Cerebral cortex The cerebral cortex, also known as the cerebral mantle, is the outer layer of neural tissue of the cerebrum of the brain in humans and other mammals. It is the largest site of Neuron, neural integration in the central nervous system, and plays ...

Cerebellum The cerebellum (: cerebella or cerebellums; Latin for 'little brain') is a major feature of the hindbrain of all vertebrates. Although usually smaller than the cerebrum, in some animals such as the mormyrid fishes it may be as large as it or eve ...

Septum In biology, a septum (Latin language, Latin for ''something that encloses''; septa) is a wall, dividing a Body cavity, cavity or structure into smaller ones. A cavity or structure divided in this way may be referred to as septate. Examples Hum ...

Whereas the α_2B adrenergic receptor is localised in the following CNS structures: * Thalamus * Pyramidal layer of the hippocampus * Cerebellar Purkinje layer and the α_2C adrenergic receptor is localised in the CNS structures: * Midbrain * Thalamus *

Amygdala The amygdala (; : amygdalae or amygdalas; also '; Latin from Greek language, Greek, , ', 'almond', 'tonsil') is a paired nucleus (neuroanatomy), nuclear complex present in the Cerebral hemisphere, cerebral hemispheres of vertebrates. It is c ...

Dorsal root ganglia A dorsal root ganglion (or spinal ganglion; also known as a posterior root ganglion) is a cluster of neurons (a ganglion) in a dorsal root of a spinal nerve. The cell bodies of sensory neurons known as first-order neurons are located in the dors ...

* Olfactory system * Hippocampus * Cerebral cortex *

Basal ganglia The basal ganglia (BG) or basal nuclei are a group of subcortical Nucleus (neuroanatomy), nuclei found in the brains of vertebrates. In humans and other primates, differences exist, primarily in the division of the globus pallidus into externa ...

Substantia nigra The substantia nigra (SN) is a basal ganglia structure located in the midbrain that plays an important role in reward and movement. ''Substantia nigra'' is Latin for "black substance", reflecting the fact that parts of the substantia nigra a ...

* Ventral tegmentum

Effects

The α₂-adrenergic receptor is classically located on vascular prejunctional terminals where it inhibits the release of norepinephrine (noradrenaline) in a form of negative feedback. It is also located on the

vascular smooth muscle Vascular smooth muscle is the type of smooth muscle that makes up most of the walls of blood vessels. Structure Vascular smooth muscle refers to the particular type of smooth muscle found within, and composing the majority of the wall of blood v ...

cells of certain blood vessels, such as those found in skin arterioles or on veins, where it sits alongside the more plentiful α₁-adrenergic receptor. The α₂-adrenergic receptor binds both norepinephrine released by sympathetic postganglionic fibers and epinephrine (adrenaline) released by the

adrenal medulla The adrenal medulla () is the inner part of the adrenal gland. It is located at the center of the gland, being surrounded by the adrenal cortex. It is the innermost part of the adrenal gland, consisting of chromaffin cells that secrete catecho ...

, binding norepinephrine with slightly higher affinity. It has several general functions in common with the α₁-adrenergic receptor, but also has specific effects of its own.

Agonists An agonist is a chemical that activates a receptor to produce a biological response. Receptors are cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an antagonist blocks the action of the agon ...

(activators) of the α₂-adrenergic receptor are frequently used in

anaesthesia Anesthesia (American English) or anaesthesia (British English) is a state of controlled, temporary loss of sensation or awareness that is induced for medical or veterinary purposes. It may include some or all of analgesia (relief from or prev ...

where they affect

sedation Sedation is the reduction of irritability or agitation by administration of sedative drugs, generally to facilitate a medical procedure or diagnostic procedure. Examples of drugs which can be used for sedation include isoflurane, diethyl ether, ...

, muscle relaxation and

analgesia Pain management is an aspect of medicine and health care involving relief of pain (pain relief, analgesia, pain control) in various dimensions, from acute and simple to chronic and challenging. Most physicians and other health professionals ...

through effects on the

(CNS). In the brain, α₂-adrenergic receptors can be localized either pre- or post-synaptically, and the majority of receptors appear to be post-synaptic. For example, the α_2A adrenergic receptor subtype is post-synaptic in the

prefrontal cortex In mammalian brain anatomy, the prefrontal cortex (PFC) covers the front part of the frontal lobe of the cerebral cortex. It is the association cortex in the frontal lobe. The PFC contains the Brodmann areas BA8, BA9, BA10, BA11, BA12, ...

and these receptors strengthen cognitive and executive functions by inhibiting cAMP opening of potassium channels, thus enhancing prefrontal connections and neuronal firing. The α_2A-adrenergic agonist,

guanfacine Guanfacine, sold under the brand name Tenex ( immediate-release) and Intuniv ( extended-release) among others, is an oral alpha-2a agonist medication used to treat attention deficit hyperactivity disorder (ADHD) and high blood pressure. Co ...

, is now used to treat prefrontal cortical cognitive disorders such as attention deficit hyperactivity disorder (ADHD).

General

Common effects include: * Suppression of release of

(

noradrenaline Norepinephrine (NE), also called noradrenaline (NA) or noradrenalin, is an organic chemical in the catecholamine family that functions in the brain and body as a hormone, neurotransmitter and neuromodulator. The name "noradrenaline" (from ...

) by negative feedback * Transient

hypertension Hypertension, also known as high blood pressure, is a Chronic condition, long-term Disease, medical condition in which the blood pressure in the artery, arteries is persistently elevated. High blood pressure usually does not cause symptoms i ...

(increase in blood pressure), followed by a sustained

hypotension Hypotension, also known as low blood pressure, is a cardiovascular condition characterized by abnormally reduced blood pressure. Blood pressure is the force of blood pushing against the walls of the arteries as the heart pumps out blood and is ...

(decrease in blood pressure) *

Vasoconstriction Vasoconstriction is the narrowing of the blood vessels resulting from contraction of the muscular wall of the vessels, in particular the large arteries and small arterioles. The process is the opposite of vasodilation, the widening of blood vesse ...

of certain

arteries An artery () is a blood vessel in humans and most other animals that takes oxygenated blood away from the heart in the systemic circulation to one or more parts of the body. Exceptions that carry deoxygenated blood are the pulmonary arteries in ...

* Vasoconstriction of arteries to

heart The heart is a muscular Organ (biology), organ found in humans and other animals. This organ pumps blood through the blood vessels. The heart and blood vessels together make the circulatory system. The pumped blood carries oxygen and nutrie ...

(

coronary artery The coronary arteries are the arterial blood vessels of coronary circulation, which transport oxygenated blood to the heart muscle. The heart requires a continuous supply of oxygen to function and survive, much like any other tissue or organ of ...

); however, the extent of this effect may be limited and may be negated by the vasodilatory effect from β₂ receptors * Constriction of some vascular smooth muscle * Venoconstriction of

veins Veins () are blood vessels in the circulatory system of humans and most other animals that carry blood towards the heart. Most veins carry deoxygenated blood from the tissues back to the heart; exceptions are those of the pulmonary and fetal c ...

* Decrease motility of

smooth muscle Smooth muscle is one of the three major types of vertebrate muscle tissue, the others being skeletal and cardiac muscle. It can also be found in invertebrates and is controlled by the autonomic nervous system. It is non- striated, so-called bec ...

gastrointestinal tract The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the Digestion, digestive system that leads from the mouth to the anus. The tract is the largest of the body's systems, after the cardiovascula ...

* Inhibition of lipolysis * Facilitation of the cognitive functions associated with the

(PFC; working memory, attention, executive functioning, etc.) * Sedation * Analgesia

Individual

Individual actions of the α₂ receptor include: * Mediates

synaptic transmission Neurotransmission (Latin: ''transmissio'' "passage, crossing" from ''transmittere'' "send, let through") is the process by which signaling molecules called neurotransmitters are released by the axon terminal of a neuron (the presynaptic neuron) ...

in pre- and postsynaptic nerve terminals ** Decrease release of

acetylcholine Acetylcholine (ACh) is an organic compound that functions in the brain and body of many types of animals (including humans) as a neurotransmitter. Its name is derived from its chemical structure: it is an ester of acetic acid and choline. Par ...

** Decrease release of

*** Inhibit norepinephrine system in brain * Inhibition of

lipolysis Lipolysis is the metabolic pathway through which lipid triglycerides are hydrolysis, hydrolyzed into a glycerol and free fatty acids. It is used to mobilize stored energy during fasting or exercise, and usually occurs in Adipose tissue, fat adip ...

adipose tissue Adipose tissue (also known as body fat or simply fat) is a loose connective tissue composed mostly of adipocytes. It also contains the stromal vascular fraction (SVF) of cells including preadipocytes, fibroblasts, Blood vessel, vascular endothel ...

* Inhibition of

insulin Insulin (, from Latin ''insula'', 'island') is a peptide hormone produced by beta cells of the pancreatic islets encoded in humans by the insulin (''INS)'' gene. It is the main Anabolism, anabolic hormone of the body. It regulates the metabol ...

release in

pancreas The pancreas (plural pancreases, or pancreata) is an Organ (anatomy), organ of the Digestion, digestive system and endocrine system of vertebrates. In humans, it is located in the abdominal cavity, abdomen behind the stomach and functions as a ...

* Induction of

glucagon Glucagon is a peptide hormone, produced by alpha cells of the pancreas. It raises the concentration of glucose and fatty acids in the bloodstream and is considered to be the main catabolic hormone of the body. It is also used as a Glucagon (medic ...

release from pancreas *

platelet aggregation Platelets or thrombocytes () are a part of blood whose function (along with the coagulation factors) is to react to bleeding from blood vessel injury by clumping to form a blood clot. Platelets have no cell nucleus; they are fragments of cytop ...

* Contraction of

sphincter A sphincter is a circular muscle that normally maintains constriction of a natural body passage or orifice and relaxes as required by normal physiological functioning. Sphincters are found in many animals. There are over 60 types in the human bo ...

s of the

* Decreased secretion from

salivary gland The salivary glands in many vertebrates including mammals are exocrine glands that produce saliva through a system of ducts. Humans have three paired major salivary glands ( parotid, submandibular, and sublingual), as well as hundreds of min ...

* Relax

(presynaptic effect) * Decreased aqueous humor fluid production from the ciliary body

Signaling cascade

The α subunit of an inhibitory

G protein G proteins, also known as guanine nucleotide-binding proteins, are a Protein family, family of proteins that act as molecular switches inside cells, and are involved in transmitting signals from a variety of stimuli outside a cell (biology), ...

- G_i dissociates from the G protein, and associates with

adenylyl cyclase Adenylate cyclase (EC 4.6.1.1, also commonly known as adenyl cyclase and adenylyl cyclase, abbreviated AC) is an enzyme with systematic name ATP diphosphate-lyase (cyclizing; 3′,5′-cyclic-AMP-forming). It catalyzes the following reaction: :A ...

. This causes the inactivation of adenylyl cyclase, resulting in a decrease of cAMP produced from ATP, which leads to a decrease of intracellular cAMP.

PKA In chemistry, an acid dissociation constant (also known as acidity constant, or acid-ionization constant; denoted ) is a quantitative measure of the strength of an acid in solution. It is the equilibrium constant for a chemical reaction :H ...

is not able to be activated by cAMP, so proteins such as phosphorylase kinase cannot be phosphorylated by PKA. In particular, phosphorylase kinase is responsible for the phosphorylation and activation of

glycogen phosphorylase Glycogen phosphorylase is one of the phosphorylase enzymes (). Glycogen phosphorylase catalyzes the rate-limiting step in glycogenolysis in animals by releasing glucose-1-phosphate from the terminal alpha-1,4-glycosidic bond. Glycogen phosphor ...

, an enzyme necessary for glycogen breakdown. Thus in this pathway, the downstream effect of adenylyl cyclase inactivation is decreased breakdown of glycogen. The relaxation of gastrointestinal tract motility is by

presynaptic In the nervous system, a synapse is a structure that allows a neuron (or nerve cell) to pass an electrical or chemical signal to another neuron or a target effector cell. Synapses can be classified as either chemical or electrical, depending o ...

inhibition, Page 163 where transmitters inhibit further release by homotropic effects. ;Agonists * 4-NEMD * 7-Me-marsanidine (also I₁

agonist An agonist is a chemical that activates a Receptor (biochemistry), receptor to produce a biological response. Receptors are Cell (biology), cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an R ...

) * Agmatine (also I

NMDA ''N''-methyl--aspartic acid, or ''N''-methyl--aspartate (NMDA), is an amino acid derivative that acts as a specific agonist at the NMDA receptor mimicking the action of glutamate, the neurotransmitter which normally acts at that receptor. Unl ...

, 5-HT₃, nicotinic

antagonist An antagonist is a character in a story who is presented as the main enemy or rival of the protagonist and is often depicted as a villain.NOS inhibitor) * Apraclonidine * Brimonidine * Cannabigerol (also acts as a moderate affinity 5-HT_1A receptor antagonist, and low affinity CB1 receptor antagonist). *

Clonidine Clonidine, sold under the brand name Catapres among others, is an α2A-adrenergic receptor agonist medication used to treat high blood pressure, attention deficit hyperactivity disorder (ADHD), drug withdrawal (e.g., alcohol, opioids, or nic ...

(also I₁

) *

Detomidine Detomidine is an imidazole derivative and Alpha-2 adrenergic receptor, α2-adrenergic receptor agonist, used as a large animal sedative, primarily used in horses. It is usually available as the salt (chemistry), salt detomidine hydrochloride. It ...

* Dexmedetomidine * Fadolmidine * Guanabenz *

Guanfacine Guanfacine, sold under the brand name Tenex ( immediate-release) and Intuniv ( extended-release) among others, is an oral alpha-2a agonist medication used to treat attention deficit hyperactivity disorder (ADHD) and high blood pressure. Co ...

* Lofexidine * Marsanidine * Medetomidine *

Methyldopa Methyldopa, also known as α-methyl-L-DOPA and sold under the brand name Aldomet among others, is a medication used for high blood pressure. It is one of the preferred treatments for high blood pressure in pregnancy. For other types of high blo ...

* Mivazerol * Rilmenidine (also I

) * Romifidine * Talipexole (also dopamine agonist) * Tiamenidine *

Tizanidine Tizanidine, sold under the brand name Zanaflex among others, is an alpha-2 (α2) adrenergic receptor agonist, similar to clonidine, that is used to treat muscle spasticity due to spinal cord injury, multiple sclerosis, and spastic cerebral ...

* Tolonidine *

Xylazine Xylazine is a structural analog of clonidine and an α2-adrenergic receptor, α2-adrenergic receptor agonist, sold under many trade names worldwide, most notably the Bayer brand name Rompun, as well as Anased, Sedazine and Chanazine. Xylazine ...

Xylometazoline Xylometazoline, also spelled xylomethazoline, is a medication used to reduce symptoms of nasal congestion, allergic rhinitis, and sinusitis. It is used directly in the nose as a spray or drops. Side effects include trouble sleeping, irritati ...

;Partial agonists *

Oxymetazoline Oxymetazoline, sold under the brand name Afrin among others, is a topical decongestant and vasoconstrictor medication. It is available over-the-counter as a nasal spray to treat nasal congestion and nosebleeds, as eye drops to treat eye rednes ...

(also α₁

) * TDIQ ;Inverse agonist *

Caffeine Caffeine is a central nervous system (CNS) stimulant of the methylxanthine chemical classification, class and is the most commonly consumed Psychoactive drug, psychoactive substance globally. It is mainly used for its eugeroic (wakefulness pr ...

( and methylxanthines) ;Antagonists * 1-PP (active metabolite of

buspirone Buspirone, sold under the brand name Buspar among others, is an anxiolytic, a medication primarily used to treat anxiety disorders, particularly generalized anxiety disorder (GAD). It is a serotonin 5-HT1A receptor, 5-HT1A receptor partial ag ...

and gepirone) *

Aripiprazole Aripiprazole, sold under the brand name Abilify, among others, is an atypical antipsychotic primarily used in the treatment of schizophrenia, bipolar disorder, and irritability associated with autism spectrum disorder; other uses include as ...

Asenapine Asenapine, sold under the brand name Saphris among others, is an atypical antipsychotic medication used to treat schizophrenia and acute mania associated with bipolar disorder as well as the medium to long-term management of bipolar disorder. I ...

* Atipamezole * Cirazoline *

Clozapine Clozapine, sold under the brand name Clozaril among others, is a psychiatric medication and was the first atypical antipsychotic to be discovered. It is used primarily to treat people with schizophrenia and schizoaffective disorder who have ...

* Efaroxan * Idazoxan * Lurasidone * Melperone * Mianserin *

Mirtazapine Mirtazapine, sold under the brand name Remeron among others, is an atypical antidepressant, atypical tetracyclic antidepressant, and as such is used primarily to treat Depression (mood), depression. Its effects may take up to four weeks but ca ...

* Napitane *

Olanzapine Olanzapine, sold under the brand name Zyprexa among others, is an atypical antipsychotic primarily used to treat schizophrenia and bipolar disorder. It is also sometimes used off-label for treatment of chemotherapy-induced nausea and vomitin ...

* Paliperidone (also primary active metabolite of

risperidone Risperidone, sold under the brand name Risperdal among others, is an atypical antipsychotic used to treat schizophrenia and bipolar disorder, as well as aggressive and self-injurious behaviors associated with autism spectrum disorder. It is t ...

) *

Phenoxybenzamine Phenoxybenzamine (PBZ, marketed under the trade names Dibenzyline and Dibenyline) is a non-selective, irreversible alpha blocker. Uses It is used in the treatment of hypertension, and specifically that caused by pheochromocytoma. It has a slowe ...

Phentolamine Phentolamine, sold under the brand name Regitine among others, is a reversible nonselective α- adrenergic antagonist. Mechanism Its primary action is vasodilation due to α1 blockade. Non-selective α-blockers can cause a much more pronounced ...

* Piribedil *

Rauwolscine Rauwolscine, also known as isoyohimbine, α-yohimbine, and corynanthidine, is an alkaloid found in various species within the genera ''Rauvolfia'' and '' Corynanthe'' (including ''Pausinystalia''). It is a stereoisomer of yohimbine. Rauwolscine ...

Risperidone Risperidone, sold under the brand name Risperdal among others, is an atypical antipsychotic used to treat schizophrenia and bipolar disorder, as well as aggressive and self-injurious behaviors associated with autism spectrum disorder. It is t ...

* Rotigotine ( α_2B antagonist, non-selective) *

Quetiapine Quetiapine ( ), sold under the brand name Seroquel among others, is an atypical antipsychotic medication used in the treatment of schizophrenia, bipolar disorder, bipolar depression, and major depressive disorder. Despite being widely prescri ...

* Norquetiapine (primary active metabolite of

quetiapine Quetiapine ( ), sold under the brand name Seroquel among others, is an atypical antipsychotic medication used in the treatment of schizophrenia, bipolar disorder, bipolar depression, and major depressive disorder. Despite being widely prescri ...

) * Setiptiline *

Tolazoline Tolazoline is a non-selective Competitive antagonist, competitive Alpha blocker#Classification, α-adrenergic receptor antagonist. It is a vasodilator that is used to treat spasms of peripheral blood vessels (as in acrocyanosis). It has also been ...

Yohimbine Yohimbine, also known as quebrachine, is an indole alkaloid derived from the bark of the African tree '' Pausinystalia johimbe'' (yohimbe); also from the bark of the unrelated South American tree '' Aspidosperma quebracho-blanco''. Yohimbine is ...

* Ziprasidone * Zotepine (discontinued)

Agonists

Norepinephrine Norepinephrine (NE), also called noradrenaline (NA) or noradrenalin, is an organic compound, organic chemical in the catecholamine family that functions in the brain and human body, body as a hormone, neurotransmitter and neuromodulator. The ...

has higher affinity for the α₂ receptor than

does, and therefore relates less to the latter's functions. Nonselective α₂ agonists include the

antihypertensive Antihypertensives are a class of drugs that are used to treat hypertension (high blood pressure). Antihypertensive therapy seeks to prevent the complications of high blood pressure, such as stroke, heart failure, kidney failure and myocardial infa ...

drug

clonidine Clonidine, sold under the brand name Catapres among others, is an α2A-adrenergic receptor agonist medication used to treat high blood pressure, attention deficit hyperactivity disorder (ADHD), drug withdrawal (e.g., alcohol, opioids, or nic ...

, which can be used to lower blood pressure and to reduce hot flashes associated with menopause. Clonidine has also been successfully used in indications that exceed what would be expected from a simple blood-pressure lowering drug: it has shown positive results in children with

ADHD Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterised by symptoms of inattention, hyperactivity, impulsivity, and emotional dysregulation that are excessive and pervasive, impairing in multiple ...

who have

tics A tic is a sudden and repetitive motor movement or vocalization that is not rhythmic and involves discrete muscle groups. Tics are typically brief and may resemble a normal behavioral characteristic or gesture. Tics can be invisible to the obs ...

resulting from the treatment with a CNS stimulant drug, such as Adderall XR or

methylphenidate Methylphenidate, sold under the brand names Ritalin ( ) and Concerta ( ) among others, is a central nervous system (CNS) stimulant used in the treatment of attention deficit hyperactivity disorder (ADHD) and narcolepsy. It may be taken Oral adm ...

; clonidine also helps alleviate symptoms of opioid withdrawal. The hypotensive effect of clonidine was initially attributed through its agonist action on presynaptic α₂ receptors, which act as a down-regulator on the amount of norepinephrine released in the

synaptic cleft Chemical synapses are biological junctions through which neurons' signals can be sent to each other and to non-neuronal cells such as those in neuromuscular junction, muscles or glands. Chemical synapses allow neurons to form biological neural ...

, an example of

autoreceptor An autoreceptor is a type of Receptor (biochemistry), receptor located in the cell membrane, membranes of neuron, nerve cells. It serves as part of a negative feedback loop in signal transduction. It is only sensitive to the neurotransmitters or ...

. However, it is now known that clonidine binds to imidazoline receptors with a much greater affinity than α₂ receptors, which would account for its applications outside the field of hypertension alone. Imidazoline receptors occur in the nucleus tractus solitarii and also the centrolateral medulla. Clonidine is now thought to decrease blood pressure via this central mechanism. Other nonselective agonists include dexmedetomidine, lofexidine (another antihypertensive), TDIQ (partial agonist),

tizanidine Tizanidine, sold under the brand name Zanaflex among others, is an alpha-2 (α2) adrenergic receptor agonist, similar to clonidine, that is used to treat muscle spasticity due to spinal cord injury, multiple sclerosis, and spastic cerebral ...

(in

spasm A spasm is a sudden involuntary contraction of a muscle, a group of muscles, or a hollow organ, such as the bladder. A spasmodic muscle contraction may be caused by many medical conditions, including dystonia. Most commonly, it is a musc ...

s, cramping) and

xylazine Xylazine is a structural analog of clonidine and an α2-adrenergic receptor, α2-adrenergic receptor agonist, sold under many trade names worldwide, most notably the Bayer brand name Rompun, as well as Anased, Sedazine and Chanazine. Xylazine ...

. Xylazine has

veterinary Veterinary medicine is the branch of medicine that deals with the prevention, management, diagnosis, and treatment of disease, disorder, and injury in non-human animals. The scope of veterinary medicine is wide, covering all animal species, both ...

use. In the European Union, dexmedetomidine received a marketing authorization from the

European Medicines Agency The European Medicines Agency (EMA) is an agency of the European Union (EU) in charge of the evaluation and supervision of pharmaceutical products. Prior to 2004, it was known as the European Agency for the Evaluation of Medicinal Products ...

(EMA) on August 10, 2012, under the brand name of Dexdor. It is indicated for sedation in the ICU for patients needing mechanical ventilation. In non-human species this is an immobilizing and anesthetic drug, presumptively also mediated by α₂ adrenergic receptors because it is reversed by yohimbine, an α₂ antagonist. α_2A selective agonists include

(an antihypertensive) and brimonidine (UK 14,304). (''R'')-3-nitrobiphenyline is an α_2C selective agonist as well as being a weak

antagonist An antagonist is a character in a story who is presented as the main enemy or rival of the protagonist and is often depicted as a villain.

Antagonists

Nonselective α blockers include, A-80426, atipamezole,

phenoxybenzamine Phenoxybenzamine (PBZ, marketed under the trade names Dibenzyline and Dibenyline) is a non-selective, irreversible alpha blocker. Uses It is used in the treatment of hypertension, and specifically that caused by pheochromocytoma. It has a slowe ...

, efaroxan, idazoxan (experimental), and SB-269,970.

is a relatively selective α₂ blocker that has been investigated as a treatment for erectile dysfunction.

Tetracyclic antidepressant Tetracyclic antidepressants (TeCAs) are a class of antidepressants that were first introduced in the 1970s. They are named after their tetracyclic chemical structure, containing four cyclic compound, rings of atoms, and are closely related to th ...

mirtazapine Mirtazapine, sold under the brand name Remeron among others, is an atypical antidepressant, atypical tetracyclic antidepressant, and as such is used primarily to treat Depression (mood), depression. Its effects may take up to four weeks but ca ...

and mianserin are also potent α antagonists with mirtazapine being more selective for α₂ subtype (~30-fold selective over α₁) than mianserin (~17-fold). α_2A selective blockers include BRL-44408 and RX-821,002. α_2B selective blockers include ARC-239 and imiloxan. α_2C selective blockers include JP-1302 and spiroxatrine, the latter also being a

serotonin Serotonin (), also known as 5-hydroxytryptamine (5-HT), is a monoamine neurotransmitter with a wide range of functions in both the central nervous system (CNS) and also peripheral tissues. It is involved in mood, cognition, reward, learning, ...

5-HT_1A antagonist.

References

External links

* {{DEFAULTSORT:Alpha-2 Adrenergic Receptor Adrenergic receptors Human proteins