A norepinephrine reuptake inhibitor (NRI, NERI) or noradrenaline reuptake inhibitor or adrenergic reuptake inhibitor (ARI), is a type of

drug A drug is any chemical substance other than a nutrient or an essential dietary ingredient, which, when administered to a living organism, produces a biological effect. Consumption of drugs can be via insufflation (medicine), inhalation, drug i ...

that acts as a reuptake inhibitor for the

neurotransmitter A neurotransmitter is a signaling molecule secreted by a neuron to affect another cell across a Chemical synapse, synapse. The cell receiving the signal, or target cell, may be another neuron, but could also be a gland or muscle cell. Neurotra ...

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) by blocking the action of the

norepinephrine transporter The norepinephrine transporter (NET), also known as noradrenaline transporter (NAT), is a protein that in humans is encoded by the solute carrier family 6 member 2 (SLC6A2) gene. NET is a monoamine transporter and is responsible for the sodium ...

(NET). This in turn leads to increased

extracellular This glossary of biology terms is a list of definitions of fundamental terms and concepts used in biology, the study of life and of living organisms. It is intended as introductory material for novices; for more specific and technical definitions ...

concentration In chemistry, concentration is the abundance of a constituent divided by the total volume of a mixture. Several types of mathematical description can be distinguished: '' mass concentration'', '' molar concentration'', '' number concentration'', ...

s of norepinephrine and epinephrine and therefore can increase

adrenergic Adrenergic means "working on adrenaline (epinephrine) or noradrenaline (norepinephrine)" (or on their receptors). When not further qualified, it is usually used in the sense of enhancing or mimicking the effects of epinephrine and norepinephrine ...

neurotransmission.

Medical use

NRIs are commonly used in the treatment of conditions like

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 ...

and

narcolepsy Narcolepsy is a chronic neurological disorder that impairs the ability to regulate sleep–wake cycles, and specifically impacts REM (rapid eye movement) sleep. The symptoms of narcolepsy include excessive daytime sleepiness (EDS), sleep-r ...

due to their

psychostimulant Stimulants (also known as central nervous system stimulants, or psychostimulants, or colloquially as uppers) are a class of drugs that increase alertness. They are used for various purposes, such as enhancing attention, motivation, cognition ...

effects and in

obesity Obesity is a medical condition, considered by multiple organizations to be a disease, in which excess Adipose tissue, body fat has accumulated to such an extent that it can potentially have negative effects on health. People are classifi ...

due to their

appetite suppressant An anorectic is a drug that reduces appetite, resulting in lower food consumption, leading to weight loss. These substances work by affecting the central nervous system or certain neurotransmitters to create a feeling of fullness or reduce the desi ...

effects. They are also frequently used as

antidepressant Antidepressants are a class of medications used to treat major depressive disorder, anxiety disorders, chronic pain, and addiction. Common side effects of antidepressants include Xerostomia, dry mouth, weight gain, dizziness, headaches, akathi ...

s for the treatment of

major depressive disorder Major depressive disorder (MDD), also known as clinical depression, is a mental disorder characterized by at least two weeks of pervasive depression (mood), low mood, low self-esteem, and anhedonia, loss of interest or pleasure in normally ...

anxiety Anxiety is an emotion characterised by an unpleasant state of inner wikt:turmoil, turmoil and includes feelings of dread over Anticipation, anticipated events. Anxiety is different from fear in that fear is defined as the emotional response ...

and

panic disorder Panic disorder is a mental disorder, specifically an anxiety disorder, characterized by reoccurring unexpected panic attacks. Panic attacks are sudden periods of intense fear that may include palpitations, sweating, shaking, shortness of breath ...

. Additionally, many addictive substances such as

cocaine Cocaine is a tropane alkaloid and central nervous system stimulant, derived primarily from the leaves of two South American coca plants, ''Erythroxylum coca'' and ''Erythroxylum novogranatense, E. novogranatense'', which are cultivated a ...

and

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 ...

possess NRI activity, though NRIs without combined dopamine reuptake inhibitor (DRI) properties are not significantly rewarding and hence are considered to have negligible potential for addiction. However, norepinephrine has been implicated as acting synergistically with dopamine when actions on the two neurotransmitters are combined (e.g., in the case of NDRIs) to produce rewarding effects in psychostimulant addictive substances.

Depression

A meta analysis published in BMJ in 2011 concluded that the selective NRI reboxetine is indistinguishable from placebo in the treatment of depression. A second review by the European Medicines Agency concluded that reboxetine was significantly more effective than placebo, and that its risk/benefit ratio was positive. The latter review, also examined the efficacy of reboxetine as a function of baseline depression, and concluded that it was effective in severe depression and panic disorder but did not show effects significantly superior to placebo in mild depression. A closely related type of drug is a norepinephrine releasing agent (NRA).

List of selective NRIs

Neurotransmitter transporters inhibitors

Many NRIs exist, including the following: * Selective norepinephrine reuptake inhibitors ** Marketed ***

Atomoxetine Atomoxetine, formerly sold under the brand name Strattera, is a selective norepinephrine reuptake inhibitor (sNRI) medication used to treat attention deficit hyperactivity disorder (ADHD) and, to a lesser extent, cognitive disengagement syndr ...

(Strattera) *** Reboxetine (Edronax, Vestra) *** Viloxazine (Qelbree, Vivalan) – but also has some other weaker activities ** Never marketed *** Amedalin (UK-3540-1) *** Daledalin (UK-3557-15) *** Edivoxetine (LY-2216684) *** Esreboxetine (AXS-14; PNU-165442G) *** Lortalamine (LM-1404) *** Nisoxetine (LY-94,939) *** Talopram (tasulopram) (Lu 3–010) *** Talsupram (Lu 5–005) *** Tandamine (AY-23,946) * NRIs with activity at other sites ** Marketed *** Bupropion (Wellbutrin, Zyban) *** Desipramine (Norpramin) *** Maprotiline (Ludiomil) *** Nortriptyline (Pamelor) *** Protriptyline (Vivactil) *** Tapentadol (Nucynta) *** Teniloxazine (Lucelan, Metatone) ** Never marketed *** Ampreloxetine (TD-9855) *** Ciclazindol (Wy-23,409) *** CP-39,332 *** Manifaxine (GW-320,659) *** Radafaxine (GW-353,162) Note: Only NRIs selective for the NET greater than the other two

monoamine transporter Monoamine transporters (MATs) are proteins that function as integral Cell membrane, plasma-membrane Neurotransmitter transporter, transporters to regulate concentrations of extracellular monoamine neurotransmitters. The three major classes are se ...

s (MATs) are listed here. For a list of NRIs that act at multiple MATs, see the other monoamine reuptake inhibitor pages such as NDRI, SNRI, and SNDRI.

References

{{Monoamine reuptake inhibitors

Medical use

Depression

List of selective NRIs

See also

References