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A '''norepinephrine reuptake inhibitor''' ('''NRI''', '''NERI''') or '''Noradrenaline reuptake inhibitor''' or '''adrenergic reuptake inhibitor''' ('''ARI'''), is a type of ] that acts as a ] for the ]s ] (noradrenaline) and ] (adrenaline) by blocking the ] of the ] (NET). This in turn leads to increased ] ]s of norepinephrine and epinephrine and therefore can increase ] ]. A '''norepinephrine reuptake inhibitor''' ('''NRI''', '''NERI''') or '''Noradrenaline reuptake inhibitor''' or '''adrenergic reuptake inhibitor''' ('''ARI'''), is a type of ] that acts as a ] for the ]s ] (noradrenaline) and ] (adrenaline) by blocking the ] of the ] (NET). This in turn leads to increased ] ]s of norepinephrine and epinephrine and therefore can increase ] ].


NRIs are commonly used in the treatment of conditions like ] and ] due to their ] effects and in ] due to their ] effects. They are also frequently used as ]s for the treatment of ], ] and ]. Additionally, many ] such as ] and ] possess NRI activity, though it is important to mention that NRIs without combined ] (DRI) properties are not significantly rewarding and hence are considered to have a negligible ].<ref name="pmid15283948">{{cite journal |vauthors=Wee S, Woolverton WL | title = Evaluation of the reinforcing effects of atomoxetine in monkeys: comparison to methylphenidate and desipramine | journal = Drug and Alcohol Dependence | volume = 75 | issue = 3 | pages = 271–6 |date=September 2004 | pmid = 15283948 | doi = 10.1016/j.drugalcdep.2004.03.010 }}</ref><ref name="pmid15526000">{{cite journal |vauthors=Gasior M, Bergman J, Kallman MJ, Paronis CA | title = Evaluation of the reinforcing effects of monoamine reuptake inhibitors under a concurrent schedule of food and i.v. drug delivery in rhesus monkeys | journal = Neuropsychopharmacology | volume = 30 | issue = 4 | pages = 758–64 |date=April 2005 | pmid = 15526000 | doi = 10.1038/sj.npp.1300593 }}</ref> However, norepinephrine has been implicated as acting synergistically with dopamine when actions on the two neurotransmitters are combined (e.g., in the case of ]s) to produce rewarding effects in psychostimulant drugs of abuse.<ref name="pmid11071707">{{cite journal |vauthors=Rothman RB, Baumann MH, Dersch CM, etal | title = Amphetamine-type central nervous system stimulants release norepinephrine more potently than they release dopamine and serotonin | journal = Synapse | volume = 39 | issue = 1 | pages = 32–41 |date=January 2001 | pmid = 11071707 | doi = 10.1002/1098-2396(20010101)39:1<32::AID-SYN5>3.0.CO;2-3 | url = }}</ref> NRIs are commonly used in the treatment of conditions like ] and ] due to their ] effects and in ] due to their ] effects. They are also frequently used as ]s for the treatment of ], ] and ]. Additionally, many ] such as ] and ] possess NRI activity, though it is important to mention that NRIs without combined ] (DRI) properties are not significantly rewarding and hence are considered to have a negligible ].<ref name="pmid15283948">{{cite journal |vauthors=Wee S, Woolverton WL | title = Evaluation of the reinforcing effects of atomoxetine in monkeys: comparison to methylphenidate and desipramine | journal = Drug and Alcohol Dependence | volume = 75 | issue = 3 | pages = 271–6 |date=September 2004 | pmid = 15283948 | doi = 10.1016/j.drugalcdep.2004.03.010 }}</ref><ref name="pmid15526000">{{cite journal |vauthors=Gasior M, Bergman J, Kallman MJ, Paronis CA | title = Evaluation of the reinforcing effects of monoamine reuptake inhibitors under a concurrent schedule of food and i.v. drug delivery in rhesus monkeys | journal = Neuropsychopharmacology | volume = 30 | issue = 4 | pages = 758–64 |date=April 2005 | pmid = 15526000 | doi = 10.1038/sj.npp.1300593 | doi-access = free }}</ref> However, norepinephrine has been implicated as acting synergistically with dopamine when actions on the two neurotransmitters are combined (e.g., in the case of ]s) to produce rewarding effects in psychostimulant drugs of abuse.<ref name="pmid11071707">{{cite journal |vauthors=Rothman RB, Baumann MH, Dersch CM, etal | title = Amphetamine-type central nervous system stimulants release norepinephrine more potently than they release dopamine and serotonin | journal = Synapse | volume = 39 | issue = 1 | pages = 32–41 |date=January 2001 | pmid = 11071707 | doi = 10.1002/1098-2396(20010101)39:1<32::AID-SYN5>3.0.CO;2-3 | url = }}</ref>


A meta analysis published in BMJ in 2011 concluded that the selective norepinephrine reuptake inhibitor ] is indistinguishable from placebo in the treatment of depression.<ref>{{cite journal |vauthors=Eyding D, Lelgemann M, Grouven U, etal |title=Reboxetine for acute treatment of major depression: systematic review and meta-analysis of published and unpublished placebo and selective serotonin reuptake inhibitor controlled trials |journal=BMJ |volume=341 |issue= |pages=c4737 |year=2010 |pmid=20940209 |pmc=2954275 |doi= 10.1136/bmj.c4737|url=}}</ref> 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.<ref>{{cite web |url=http://www.mhra.gov.uk/home/groups/pl-p/documents/websiteresources/con129107.pdf |title=MHRA Public Assessment Report |accessdate=2014-04-26 }}</ref> A meta analysis published in BMJ in 2011 concluded that the selective norepinephrine reuptake inhibitor ] is indistinguishable from placebo in the treatment of depression.<ref>{{cite journal |vauthors=Eyding D, Lelgemann M, Grouven U, etal |title=Reboxetine for acute treatment of major depression: systematic review and meta-analysis of published and unpublished placebo and selective serotonin reuptake inhibitor controlled trials |journal=BMJ |volume=341 |issue= |pages=c4737 |year=2010 |pmid=20940209 |pmc=2954275 |doi= 10.1136/bmj.c4737|url=}}</ref> 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.<ref>{{cite web |url=http://www.mhra.gov.uk/home/groups/pl-p/documents/websiteresources/con129107.pdf |title=MHRA Public Assessment Report |accessdate=2014-04-26 }}</ref>

Revision as of 04:27, 13 April 2020

Norepinephrine reuptake inhibitor
Drug class
Synonymsadrenergic reuptake inhibitor
External links
MeSHD018759
Legal status
In Wikidata
Norepinephrine
Epinephrine

A norepinephrine reuptake inhibitor (NRI, NERI) or Noradrenaline reuptake inhibitor or adrenergic reuptake inhibitor (ARI), is a type of drug that acts as a reuptake inhibitor for the neurotransmitters norepinephrine (noradrenaline) and epinephrine (adrenaline) by blocking the action of the norepinephrine transporter (NET). This in turn leads to increased extracellular concentrations of norepinephrine and epinephrine and therefore can increase adrenergic neurotransmission.

NRIs are commonly used in the treatment of conditions like ADHD and narcolepsy due to their psychostimulant effects and in obesity due to their appetite suppressant effects. They are also frequently used as antidepressants for the treatment of major depressive disorder, anxiety and panic disorder. Additionally, many drugs of abuse such as cocaine and methylphenidate possess NRI activity, though it is important to mention that NRIs without combined dopamine reuptake inhibitor (DRI) properties are not significantly rewarding and hence are considered to have a negligible abuse potential. 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 drugs of abuse.

A meta analysis published in BMJ in 2011 concluded that the selective norepinephrine reuptake inhibitor 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
  Noradrenaline (norepinephrine) transporter inhibitors

Many NRIs exist, including the following:

Note: Only NRIs selective for the NET greater than the other two monoamine transporters (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.

See also

References

  1. Wee S, Woolverton WL (September 2004). "Evaluation of the reinforcing effects of atomoxetine in monkeys: comparison to methylphenidate and desipramine". Drug and Alcohol Dependence. 75 (3): 271–6. doi:10.1016/j.drugalcdep.2004.03.010. PMID 15283948.
  2. Gasior M, Bergman J, Kallman MJ, Paronis CA (April 2005). "Evaluation of the reinforcing effects of monoamine reuptake inhibitors under a concurrent schedule of food and i.v. drug delivery in rhesus monkeys". Neuropsychopharmacology. 30 (4): 758–64. doi:10.1038/sj.npp.1300593. PMID 15526000.
  3. Rothman RB, Baumann MH, Dersch CM, et al. (January 2001). "Amphetamine-type central nervous system stimulants release norepinephrine more potently than they release dopamine and serotonin". Synapse. 39 (1): 32–41. doi:10.1002/1098-2396(20010101)39:1<32::AID-SYN5>3.0.CO;2-3. PMID 11071707.
  4. Eyding D, Lelgemann M, Grouven U, et al. (2010). "Reboxetine for acute treatment of major depression: systematic review and meta-analysis of published and unpublished placebo and selective serotonin reuptake inhibitor controlled trials". BMJ. 341: c4737. doi:10.1136/bmj.c4737. PMC 2954275. PMID 20940209.
  5. "MHRA Public Assessment Report" (PDF). Retrieved 2014-04-26.
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Related articles
Antidepressants (N06A)
Specific reuptake inhibitors and/or receptor modulators
SSRIsTooltip Selective serotonin reuptake inhibitors
SNRIsTooltip Serotonin–norepinephrine reuptake inhibitors
NRIsTooltip Norepinephrine reuptake inhibitors
NDRIsTooltip Norepinephrine–dopamine reuptake inhibitors
NaSSAsTooltip Noradrenergic and specific serotonergic antidepressants
SARIsTooltip Serotonin antagonist and reuptake inhibitors
SMSTooltip Serotonin modulator and stimulators
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Tricyclic and tetracyclic antidepressants
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(NRIsTooltip Norepinephrine reuptake inhibitors)
SERTTooltip Serotonin transporter
(SRIsTooltip Serotonin reuptake inhibitors)
VMATsTooltip Vesicular monoamine transporters
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See also: Receptor/signaling modulatorsMonoamine releasing agentsAdrenergicsDopaminergicsSerotonergicsMonoamine metabolism modulatorsMonoamine neurotoxins
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