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{{Short description|Drug class}} |
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A '''monoamine reuptake inhibitor''' ('''MRI''')<ref name="pmid20200509">{{cite journal |vauthors=Axel AM, Mikkelsen JD, Hansen HH | title = Tesofensine, a novel triple monoamine reuptake inhibitor, induces appetite suppression by indirect stimulation of alpha1 adrenoceptor and dopamine D1 receptor pathways in the diet-induced obese rat | journal = Neuropsychopharmacology | volume = 35 | issue = 7 | pages = 1464–76 |date=June 2010 | pmid = 20200509 | pmc = 3055463 | doi = 10.1038/npp.2010.16 }}</ref> is a [[drug]] that acts as a [[reuptake inhibitor]] of one or more of the three major [[monoamine neurotransmitter]]s [[serotonin]], [[norepinephrine]], and [[dopamine]] by blocking the action of one or more of the respective [[monoamine transporter]]s (MATs), which include the [[serotonin transporter]] (SERT), [[norepinephrine transporter]] (NET), and [[dopamine transporter]] (DAT). This in turn results in an increase in the [[synapse|synaptic]] [[concentration]]s of one or more of these neurotransmitters and therefore an increase in [[monoaminergic]] [[neurotransmission]]. |
A '''monoamine reuptake inhibitor''' ('''MRI''')<ref name="pmid20200509">{{cite journal |vauthors=Axel AM, Mikkelsen JD, Hansen HH | title = Tesofensine, a novel triple monoamine reuptake inhibitor, induces appetite suppression by indirect stimulation of alpha1 adrenoceptor and dopamine D1 receptor pathways in the diet-induced obese rat | journal = Neuropsychopharmacology | volume = 35 | issue = 7 | pages = 1464–76 |date=June 2010 | pmid = 20200509 | pmc = 3055463 | doi = 10.1038/npp.2010.16 }}</ref> is a [[drug]] that acts as a [[reuptake inhibitor]] of one or more of the three major [[monoamine neurotransmitter]]s [[serotonin]], [[norepinephrine]], and [[dopamine]] by blocking the action of one or more of the respective [[monoamine transporter]]s (MATs), which include the [[serotonin transporter]] (SERT), [[norepinephrine transporter]] (NET), and [[dopamine transporter]] (DAT). This in turn results in an increase in the [[synapse|synaptic]] [[concentration]]s of one or more of these neurotransmitters and therefore an increase in [[monoaminergic]] [[neurotransmission]]. |
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==Uses== |
==Uses== |
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The majority of currently approved [[antidepressant]]s act predominantly or exclusively as MRIs, including the [[selective serotonin reuptake inhibitor]]s (SSRIs), [[serotonin–norepinephrine reuptake inhibitor]]s (SNRIs), and almost all of the [[tricyclic antidepressant]]s (TCAs).<ref name="FinkelClark2008">{{cite book | author1 = Richard Finkel | author2 = Michelle Alexia Clark | author3 = Pamela C. Champe |author4=Luigi X. Cubeddu | title = Lippincott's Illustrated Reviews: Pharmacology | url = https://books.google.com/books?id=Q4hG2gRhy7oC&pg=PA141 | |
The majority of currently approved [[antidepressant]]s act predominantly or exclusively as MRIs, including the [[selective serotonin reuptake inhibitor]]s (SSRIs), [[serotonin–norepinephrine reuptake inhibitor]]s (SNRIs), and almost all of the [[tricyclic antidepressant]]s (TCAs).<ref name="FinkelClark2008">{{cite book | author1 = Richard Finkel | author2 = Michelle Alexia Clark | author3 = Pamela C. Champe |author4=Luigi X. Cubeddu | title = Lippincott's Illustrated Reviews: Pharmacology | url = https://books.google.com/books?id=Q4hG2gRhy7oC&pg=PA141 | access-date = 12 May 2012 | date = 16 July 2008 | publisher = Lippincott Williams & Wilkins | isbn = 978-0-7817-7155-9 | page = 141}}</ref> Many [[psychostimulant]]s used either in the treatment of {{abbrlink|ADHD|attention-deficit hyperactivity disorder}} or as [[appetite suppressant]]s in the treatment of [[obesity]] also behave as MRIs, although notably amphetamine (and methamphetamine), which do act to some extent as monoamine reuptake inhibitors, exerts their effects primarily as releasing agents.<ref>{{Cite journal|last1=Walker|first1=Q. David|last2=Morris|first2=Sarah E.|last3=Arrant|first3=Andrew E.|last4=Nagel|first4=Jacqueline M.|last5=Parylak|first5=Sarah|last6=Zhou|first6=Guiying|last7=Caster|first7=Joseph M.|last8=Kuhn|first8=Cynthia M.|date=October 2010|title=Dopamine Uptake Inhibitors but Not Dopamine Releasers Induce Greater Increases in Motor Behavior and Extracellular Dopamine in Adolescent Rats Than in Adult Male Rats|journal=The Journal of Pharmacology and Experimental Therapeutics|volume=335|issue=1|pages=124–132|doi=10.1124/jpet.110.167320|issn=0022-3565|pmc=2957786|pmid=20605908}}</ref><ref name="OffermannsRosenthal2008">{{cite book | author1 = Stefan Offermanns | author2 = Walter Rosenthal | title = Encyclopedia of Molecular Pharmacology | url = https://books.google.com/books?id=fGe6NDIGQpsC&pg=PA1039 | access-date = 12 May 2012 | year = 2008 | publisher = Springer | isbn = 978-3-540-38916-3 | page = 1039}}</ref> Additionally, psychostimulants acting as MRIs that affect dopamine such as [[cocaine]] and [[methylphenidate]] are often [[drug abuse|abused]] as [[recreational drug]]s.<ref name="RuizStrain2011">{{cite book | author1 = Pedro Ruiz | author2 = Eric C. Strain | title = Lowinson and Ruiz's Substance Abuse: A Comprehensive Textbook | url = https://books.google.com/books?id=w4ZUJAdleTsC&pg=PA55 | access-date = 12 May 2012 | date = 15 April 2011 | publisher = Lippincott Williams & Wilkins | isbn = 978-1-60547-277-5 | page = 55}}</ref> As a result, many of them have become [[controlled substance]]s, which in turn has resulted in the [[Clandestine chemistry|clandestine synthesis]] of a vast array of [[designer drug]]s for the purpose of bypassing [[drug prohibition law|drug law]]s; a prime example of such is the mixed monoamine reuptake inhibitor and [[monoamine releasing agent|releasing agent]] [[mephedrone]].<ref name="pmid21810934">{{cite journal |vauthors=Hadlock GC, Webb KM, McFadden LM, etal | title = 4-Methylmethcathinone (mephedrone): neuropharmacological effects of a designer stimulant of abuse | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 339 | issue = 2 | pages = 530–6 |date=November 2011 | pmid = 21810934 | doi = 10.1124/jpet.111.184119 | pmc = 3200001}}</ref> |
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==Types of MRIs== |
==Types of MRIs== |
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* Specific for one monoamine transporter |
* Specific for one monoamine transporter |
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** [[Serotonin reuptake inhibitor]] (SRI) |
** [[Serotonin reuptake inhibitor]] (SRI) |
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*** |
*** [[Selective serotonin reuptake inhibitor]] (SSRI) |
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** [[Norepinephrine reuptake inhibitor]] (NRI) |
** [[Norepinephrine reuptake inhibitor]] (NRI) |
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*** [[Selective norepinephrine reuptake inhibitor]] (sNRI) |
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** [[Dopamine reuptake inhibitor]] (DRI) |
** [[Dopamine reuptake inhibitor]] (DRI) |
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* Non-specific, binding to two or more monoamine transporters |
* Non-specific, binding to two or more monoamine transporters |
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{| class="wikitable sortable" style="text-align:left; font-size:small;" |
{| class="wikitable sortable" style="text-align:left; font-size:small;" |
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|+ Binding profiles of {{abbr|MRIs|monoamine reuptake inhibitors}} at human {{abbr|MATs|monoamine transporters}}<ref name="pmid9537821">{{cite journal | vauthors = Tatsumi M, Groshan K, Blakely RD, Richelson E | title = Pharmacological profile of antidepressants and related compounds at human monoamine transporters | journal = Eur. J. Pharmacol. | volume = 340 | issue = 2–3 | pages = 249–58 | year = 1997 | pmid = 9537821 | doi = 10.1016/s0014-2999(97)01393-9| url = https://www.academia.edu/download/45762636/s0014-2999_2897_2901393-920160518-31441-t07hp6.pdf}}</ref> |
|+ Binding profiles of {{abbr|MRIs|monoamine reuptake inhibitors}} at human {{abbr|MATs|monoamine transporters}}<ref name="pmid9537821">{{cite journal | vauthors = Tatsumi M, Groshan K, Blakely RD, Richelson E | title = Pharmacological profile of antidepressants and related compounds at human monoamine transporters | journal = Eur. J. Pharmacol. | volume = 340 | issue = 2–3 | pages = 249–58 | year = 1997 | pmid = 9537821 | doi = 10.1016/s0014-2999(97)01393-9| url = https://www.academia.edu/download/45762636/s0014-2999_2897_2901393-920160518-31441-t07hp6.pdf}}{{dead link|date=July 2022|bot=medic}}{{cbignore|bot=medic}}</ref> |
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! Compound !! {{abbrlink|SERT|Serotonin transporter}} !! {{abbrlink|NET|Norepinephrine transporter}} !! {{abbrlink|DAT|Dopamine transporter}} !! Type !! Class |
! Compound !! {{abbrlink|SERT|Serotonin transporter}} !! {{abbrlink|NET|Norepinephrine transporter}} !! {{abbrlink|DAT|Dopamine transporter}} !! Type !! Class |
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| [[Amfonelic acid]] || {{abbr|ND|No data}} || {{abbr|ND|No data}} || 207 || DRI || Stimulant |
| [[Amfonelic acid]] || {{abbr|ND|No data}} || {{abbr|ND|No data}} || 207 || DRI || Stimulant |
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| [[Amineptine]]*<ref name="pmid3708219">{{cite journal | vauthors = Ceci A, Garattini S, Gobbi M, Mennini T | title = Effect of long term amineptine treatment on pre- and postsynaptic mechanisms in rat brain | journal = Br. J. Pharmacol. | volume = 88 | issue = 1 | pages = 269–75 | year = 1986 | pmid = 3708219 | pmc = 1917102 | doi = 10.1111/j.1476-5381.1986.tb09495.x |
| [[Amineptine]]*<ref name="pmid3708219">{{cite journal | vauthors = Ceci A, Garattini S, Gobbi M, Mennini T | title = Effect of long term amineptine treatment on pre- and postsynaptic mechanisms in rat brain | journal = Br. J. Pharmacol. | volume = 88 | issue = 1 | pages = 269–75 | year = 1986 | pmid = 3708219 | pmc = 1917102 | doi = 10.1111/j.1476-5381.1986.tb09495.x}}</ref><ref name="pmid2698268">{{cite journal |vauthors=Garattini S, Mennini T |title=Pharmacology of amineptine: synthesis and updating |journal=Clin Neuropharmacol |volume=12 Suppl 2 |pages=S13–8 |year=1989 |pmid=2698268 |doi= 10.1097/00002826-198912002-00003|s2cid=10947713 }}</ref> || >100,000 (rat) || 10,000 (rat) || 1,000–1,400 (rat) || DRI || Stimulant |
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| [[Amitriptyline]] || 4.30 || 35 || 3,250 || SNRI || TCA |
| [[Amitriptyline]] || 4.30 || 35 || 3,250 || SNRI || TCA |
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| [[Amoxapine]] || 58 || 16.0 || 4,310 || SNRI || {{abbr|TeCA|Tetracyclic antidepressant}} |
| [[Amoxapine]] || 58 || 16.0 || 4,310 || SNRI || {{abbr|TeCA|Tetracyclic antidepressant}} |
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| [[ |
| [[Amphetamine]] || >100,000 || {{abbr|ND|No data}} || {{abbr|ND|No data}} || {{abbr|NDRA|Norepinephrine–dopamine releasing agent}} || Stimulant |
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| [[ |
| [[D-Amphetamine]] || >100,000 || 530 || 2,900 || NDRA || Stimulant |
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⚫ | | [[L-Amphetamine]] || >100,000 || {{abbr|ND|No data}} || {{abbr|ND|No data}} || {{abbr|NRA|Norepinephrine releasing agent}} || Stimulant |
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| [[Bupropion]] || 9,100 || 52,000 || 520 || NDRI || Stimulant |
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| [[Butriptyline]] || 1,360 || 5,100 || 3,940 || N/A ({{abbr|IA|inactive}}) || TCA |
| [[Butriptyline]] || 1,360 || 5,100 || 3,940 || N/A ({{abbr|IA|inactive}}) || TCA |
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| [[Citalopram]] || 1.16 || 4,070 || 28,100 || SRI || {{abbr|SSRI|Selective serotonin reuptake inhibitor}} |
| [[Citalopram]] || 1.16 || 4,070 || 28,100 || SRI || {{abbr|SSRI|Selective serotonin reuptake inhibitor}} |
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⚫ | | [[Escitalopram]]<ref name="pmid12232544">{{cite journal | vauthors = Owens JM, Knight DL, Nemeroff CB | title = [Second generation SSRIS: human monoamine transporter binding profile of escitalopram and R-fluoxetine] | language = fr | journal = Encephale | volume = 28 | issue = 4 | pages = 350–5 | year = 2002 | pmid = 12232544 }}</ref> || 1.1 || 7,841 || 27,410 || SRI || SSRI |
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| [[Clomipramine]] || 0.28 || 38 || 2,190 || SNRI || TCA |
| [[Clomipramine]] || 0.28 || 38 || 2,190 || SNRI || TCA |
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| [[Cocaethylene]]<ref name="pmid14612135">{{cite journal | vauthors = Rothman RB, Baumann MH | title = Monoamine transporters and psychostimulant drugs | journal = Eur. J. Pharmacol. | volume = 479 | issue = 1–3 | pages = 23–40 | year = 2003 | pmid = 14612135 | doi = 10.1016/j.ejphar.2003.08.054 |
| [[Cocaethylene]]<ref name="pmid14612135">{{cite journal | vauthors = Rothman RB, Baumann MH | title = Monoamine transporters and psychostimulant drugs | journal = Eur. J. Pharmacol. | volume = 479 | issue = 1–3 | pages = 23–40 | year = 2003 | pmid = 14612135 | doi = 10.1016/j.ejphar.2003.08.054}}</ref> || 3,878 || >10,000 || 555 || SDRI || Stimulant |
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| [[Cocaine]]<ref name="pmid14612135" /> || 304 || 779 || 478 || SNDRI || Stimulant |
| [[Cocaine]]<ref name="pmid14612135" /> || 304 || 779 || 478 || SNDRI || Stimulant |
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| [[Cocaine]] |
| [[Cocaine]]<ref>http://www.emcdda.europa.eu/system/files/publications/1814/TDAS15001ENN.pdf {{Bare URL PDF|date=March 2022}}</ref> || 313±17 (IC<sub>50</sub>) || 292±34 (IC<sub>50</sub>) || 211±19 (IC<sub>50</sub>) || SNDRI || Stimulant |
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| [[Desipramine]] || 17.6 || 0.83 || 3,190 || SNRI || TCA |
| [[Desipramine]] || 17.6 || 0.83 || 3,190 || SNRI || TCA |
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| [[Desmethylsertraline]] || 3.0 || 390 || 129 || SRI || SSRI |
| [[Desmethylsertraline]] || 3.0 || 390 || 129 || SRI || SSRI |
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| [[Desmethylsibutramine]]<ref name="pmid12119986">{{cite journal | vauthors = Nisoli E, Carruba MO | title = An assessment of the safety and efficacy of sibutramine, an anti-obesity drug with a novel mechanism of action | journal = Obes Rev | volume = 1 | issue = 2 | pages = 127–39 | year = 2000 | pmid = 12119986 | doi = 10.1046/j.1467-789x.2000.00020.x| |
| [[Desmethylsibutramine]]<ref name="pmid12119986">{{cite journal | vauthors = Nisoli E, Carruba MO | title = An assessment of the safety and efficacy of sibutramine, an anti-obesity drug with a novel mechanism of action | journal = Obes Rev | volume = 1 | issue = 2 | pages = 127–39 | year = 2000 | pmid = 12119986 | doi = 10.1046/j.1467-789x.2000.00020.x| s2cid = 20553857 }}</ref> || 15 || 20 || 49 || SNDRI || SNRI |
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| [[Desmethylsibutramine|(''R'')-Desmethylsibutramine]] || 44 || 4 || 12 || SNDRI || SNRI |
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| [[Desoxypipradrol]]<ref name="pmid23261499">{{cite journal | vauthors = Iversen L, Gibbons S, Treble R, Setola V, Huang XP, Roth BL | title = Neurochemical profiles of some novel psychoactive substances | journal = Eur. J. Pharmacol. | volume = 700 | issue = 1–3 | pages = 147–51 | year = 2013 | pmid = 23261499 | pmc = 3582025 | doi = 10.1016/j.ejphar.2012.12.006 |
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| [[Desmethylsibutramine|(''S'')-Desmethylsibutramine]] || 9,200 || 870 || 180 || SNDRI || SNRI |
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| [[Desvenlafaxine]]*<ref name="pmid16675639">{{cite journal | vauthors = Deecher DC, Beyer CE, Johnston G, Bray J, Shah S, Abou-Gharbia M, Andree TH | title = Desvenlafaxine succinate: A new serotonin and norepinephrine reuptake inhibitor | journal = J. Pharmacol. Exp. Ther. | volume = 318 | issue = 2 | pages = 657–65 | year = 2006 | pmid = 16675639 | doi = 10.1124/jpet.106.103382 | |
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⚫ | | [[Desoxypipradrol]]<ref name="pmid23261499">{{cite journal|author6-link=Bryan Roth | vauthors = Iversen L, Gibbons S, Treble R, Setola V, Huang XP, Roth BL | title = Neurochemical profiles of some novel psychoactive substances | journal = Eur. J. Pharmacol. | volume = 700 | issue = 1–3 | pages = 147–51 | year = 2013 | pmid = 23261499 | pmc = 3582025 | doi = 10.1016/j.ejphar.2012.12.006 }}</ref> || 53,700 || 550 || 50 || NDRI || Stimulant |
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⚫ | | [[Desvenlafaxine]]*<ref name="pmid16675639">{{cite journal | vauthors = Deecher DC, Beyer CE, Johnston G, Bray J, Shah S, Abou-Gharbia M, Andree TH | title = Desvenlafaxine succinate: A new serotonin and norepinephrine reuptake inhibitor | journal = J. Pharmacol. Exp. Ther. | volume = 318 | issue = 2 | pages = 657–65 | year = 2006 | pmid = 16675639 | doi = 10.1124/jpet.106.103382 | s2cid = 15063064 }}</ref> || 47 || 531 || {{abbr|ND|No data}} || SNRI || SNRI |
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| [[Didesmethylsibutramine]]<ref name="pmid12119986" /> || 20 || 15 || 45 || SNDRI || SNRI |
| [[Didesmethylsibutramine]]<ref name="pmid12119986" /> || 20 || 15 || 45 || SNDRI || SNRI |
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| [[Didesmethylsibutramine|(''R'')-Didesmethylsibutramine]] || 140 || 13 || 8.9 || SNDRI || SNRI |
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| [[Didesmethylsibutramine|(''S'')-Didesmethylsibutramine]] || 4,300 || 62 || 12 || SNDRI || SNRI |
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| [[Diphenhydramine]] || 3,800 || 960 || 2,200 || N/A ({{abbr|IA|inactive}}) || Antihistamine |
| [[Diphenhydramine]] || 3,800 || 960 || 2,200 || N/A ({{abbr|IA|inactive}}) || Antihistamine |
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| [[Doxepin]] || 68 || 29.5 || 12,100 || SNRI || TCA |
| [[Doxepin]] || 68 || 29.5 || 12,100 || SNRI || TCA |
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| [[Duloxetine]]*<ref name="pmid14744476">{{cite journal | vauthors = Vaishnavi SN, Nemeroff CB, Plott SJ, Rao SG, Kranzler J, Owens MJ | title = Milnacipran: a comparative analysis of human monoamine uptake and transporter binding affinity | journal = Biol. Psychiatry | volume = 55 | issue = 3 | pages = 320–2 | year = 2004 | pmid = 14744476 | doi = 10.1016/j.biopsych.2003.07.006 }}</ref> || 3.7 || 20 || 439 || SNRI || SNRI |
| [[Duloxetine]]*<ref name="pmid14744476">{{cite journal | vauthors = Vaishnavi SN, Nemeroff CB, Plott SJ, Rao SG, Kranzler J, Owens MJ | title = Milnacipran: a comparative analysis of human monoamine uptake and transporter binding affinity | journal = Biol. Psychiatry | volume = 55 | issue = 3 | pages = 320–2 | year = 2004 | pmid = 14744476 | doi = 10.1016/j.biopsych.2003.07.006 | s2cid = 29448095 }}</ref> || 3.7 || 20 || 439 || SNRI || SNRI |
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| [[Escitalopram]]<ref name="pmid12232544">{{cite journal | vauthors = Owens JM, Knight DL, Nemeroff CB | title = [Second generation SSRIS: human monoamine transporter binding profile of escitalopram and R-fluoxetine] | language = |
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| [[Etoperidone]] || 890 || 20,000 || 52,000 || SRI || {{abbr|SARI|Serotonin antagonist and reuptake inhibitor}} |
| [[Etoperidone]] || 890 || 20,000 || 52,000 || SRI || {{abbr|SARI|Serotonin antagonist and reuptake inhibitor}} |
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| [[GBR-12935]]<ref name="pmid14612135" /> || 289 || 277 || 4.90 || DRI || Stimulant |
| [[GBR-12935]]<ref name="pmid14612135" /> || 289 || 277 || 4.90 || DRI || Stimulant |
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⚫ | | [[Hydroxybupropion]]<ref>{{cite journal |last1=Damaj |first1=MI |last2=Carroll |first2=FI |last3=Eaton |first3=JB |last4=Navarro |first4=HA |last5=Blough |first5=BE |last6=Mirza |first6=S |last7=Lukas |first7=RJ |last8=Martin |first8=BR |title=Enantioselective effects of hydroxy metabolites of bupropion on behavior and on function of monoamine transporters and nicotinic receptors. |journal=Molecular Pharmacology |date=September 2004 |volume=66 |issue=3 |pages=675–82 |doi=10.1124/mol.104.001313 |pmid=15322260 |s2cid=1577336 }}</ref> || {{abbr|ND|No data}} || 1.7 (IC<sub>50</sub>) || >10 (IC<sub>50</sub>) || NDRI || Stimulant |
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| [[Imipramine]] || 1.40 || 37 || 8,500 || SNRI || TCA |
| [[Imipramine]] || 1.40 || 37 || 8,500 || SNRI || TCA |
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| [[Iprindole]] || 1,620 || 1,262 || 6,530 || N/A ({{abbr|IA|inactive}}) || TCA |
| [[Iprindole]] || 1,620 || 1,262 || 6,530 || N/A ({{abbr|IA|inactive}}) || TCA |
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| [[Levomilnacipran]]*<ref name="pmid23499664">{{cite journal | vauthors = Auclair AL, Martel JC, Assié MB, Bardin L, Heusler P, Cussac D, Marien M, Newman-Tancredi A, O'Connor JA, Depoortère R | title = Levomilnacipran (F2695), a norepinephrine-preferring SNRI: profile in vitro and in models of depression and anxiety | journal = Neuropharmacology | volume = 70 |
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| [[Lofepramine]] || 70 || 5.4 || 18,000 || SNRI || TCA |
| [[Lofepramine]] || 70 || 5.4 || 18,000 || SNRI || TCA |
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| [[Mazindol]] || 39 || 0.45 || 8.1 || NDRI || Stimulant |
| [[Mazindol]] || 39 || 0.45 || 8.1 || NDRI || Stimulant |
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| {{abbrlink|MDPV|Methylenedioxypyrovalerone}}<ref name="pmid23072836">{{cite journal | vauthors = Baumann MH, Partilla JS, Lehner KR, Thorndike EB, Hoffman AF, Holy M, Rothman RB, Goldberg SR, Lupica CR, Sitte HH, Brandt SD, Tella SR, Cozzi NV, Schindler CW | title = Powerful cocaine-like actions of 3,4-methylenedioxypyrovalerone (MDPV), a principal constituent of psychoactive 'bath salts' products | journal = Neuropsychopharmacology | volume = 38 | issue = 4 | pages = 552–62 | year = 2013 | pmid = 23072836 | pmc = 3572453 | doi = 10.1038/npp.2012.204 |
| {{abbrlink|MDPV|Methylenedioxypyrovalerone}}<ref name="pmid23072836">{{cite journal | vauthors = Baumann MH, Partilla JS, Lehner KR, Thorndike EB, Hoffman AF, Holy M, Rothman RB, Goldberg SR, Lupica CR, Sitte HH, Brandt SD, Tella SR, Cozzi NV, Schindler CW | title = Powerful cocaine-like actions of 3,4-methylenedioxypyrovalerone (MDPV), a principal constituent of psychoactive 'bath salts' products | journal = Neuropsychopharmacology | volume = 38 | issue = 4 | pages = 552–62 | year = 2013 | pmid = 23072836 | pmc = 3572453 | doi = 10.1038/npp.2012.204 }}</ref> || 3,349 || 26 || 4.1 || NDRI || Stimulant |
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| [[ |
| [[Methamphetamine]] || >100,000 || {{abbr|ND|No data}} || {{abbr|ND|No data}} || NDRA || Stimulant |
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| [[D-Methamphetamine]] || >100,000 || 660 || 2,800 || NDRA || Stimulant |
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| [[Levomethamphetamine|L-Methamphetamine]] || >100,000 || {{abbr|ND|No data}} || {{abbr|ND|No data}} || NRA || Stimulant |
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| [[Methylphenidate]] || >10,000 || 788 || 121 || NDRI || Stimulant |
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| [[Dexmethylphenidate|D-Methylphenidate]] || >10,000 || 206 || 161 || NDRI || Stimulant |
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| [[Methylphenidate#Pharmacodynamics|L-Methylphenidate]] || >6,700 || >10,000 || 2,250 || NDRI || Stimulant |
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| [[Mianserin]] || 4,000 || 71 || 9,400 || NRI || TeCA |
| [[Mianserin]] || 4,000 || 71 || 9,400 || NRI || TeCA |
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| [[Milnacipran]]*<ref name="pmid14744476" /> || 151 || 68 || >100,000 || SNRI || SNRI |
| [[Milnacipran]]*<ref name="pmid14744476" /> || 151 || 68 || >100,000 || SNRI || SNRI |
||
|- |
|||
⚫ | | [[Levomilnacipran]]*<ref name="pmid23499664">{{cite journal | vauthors = Auclair AL, Martel JC, Assié MB, Bardin L, Heusler P, Cussac D, Marien M, Newman-Tancredi A, O'Connor JA, Depoortère R | title = Levomilnacipran (F2695), a norepinephrine-preferring SNRI: profile in vitro and in models of depression and anxiety | journal = Neuropharmacology | volume = 70 | pages = 338–47 | year = 2013 | pmid = 23499664 | doi = 10.1016/j.neuropharm.2013.02.024 | doi-access = free }}</ref> || 19.0 || 10.5 || >100,000 || SNRI || SNRI |
||
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|- |
||
| [[Mirtazapine]] || >100,000 || 4,600 || >100,000 || N/A ({{abbr|IA|inactive}}) || TeCA |
| [[Mirtazapine]] || >100,000 || 4,600 || >100,000 || N/A ({{abbr|IA|inactive}}) || TeCA |
||
|- |
|- |
||
| [[Modafinil]]*<ref name="pmid19197004">{{cite journal | vauthors = Zolkowska D, Jain R, Rothman RB, Partilla JS, Roth BL, Setola V, Prisinzano TE, Baumann MH | title = Evidence for the involvement of dopamine transporters in behavioral stimulant effects of modafinil | journal = J. Pharmacol. Exp. Ther. | volume = 329 | issue = 2 | pages = 738–46 | year = 2009 | pmid = 19197004 | pmc = 2672878 | doi = 10.1124/jpet.108.146142 |
| [[Modafinil]]*<ref name="pmid19197004">{{cite journal | vauthors = Zolkowska D, Jain R, Rothman RB, Partilla JS, Roth BL, Setola V, Prisinzano TE, Baumann MH | title = Evidence for the involvement of dopamine transporters in behavioral stimulant effects of modafinil | journal = J. Pharmacol. Exp. Ther. | volume = 329 | issue = 2 | pages = 738–46 | year = 2009 | pmid = 19197004 | pmc = 2672878 | doi = 10.1124/jpet.108.146142 }}</ref> || >50,000 || 136,000 || 4,043 || DRI || Stimulant |
||
|- |
|- |
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| [[Nefazodone]] || 200 || 360 || 360 || SNDRI || SARI |
| [[Nefazodone]] || 200 || 360 || 360 || SNDRI || SARI |
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|- |
|- |
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| [[Nefopam]]<ref name="pmid22711801">{{cite journal | vauthors = Gregori-Puigjané E, Setola V, Hert J, Crews BA, Irwin JJ, Lounkine E, Marnett L, Roth BL, Shoichet BK | title = Identifying mechanism-of-action targets for drugs and probes | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 109 | issue = 28 | pages = 11178–83 | year = 2012 | pmid = 22711801 | pmc = 3396511 | doi = 10.1073/pnas.1204524109 | |
| [[Nefopam]]<ref name="pmid22711801">{{cite journal | vauthors = Gregori-Puigjané E, Setola V, Hert J, Crews BA, Irwin JJ, Lounkine E, Marnett L, Roth BL, Shoichet BK | title = Identifying mechanism-of-action targets for drugs and probes | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 109 | issue = 28 | pages = 11178–83 | year = 2012 | pmid = 22711801 | pmc = 3396511 | doi = 10.1073/pnas.1204524109 | bibcode = 2012PNAS..10911178G | doi-access = free }}</ref> || 29 || 33 || 531 || SNDRI || Analgesic |
||
|- |
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| [[Nisoxetine]]<ref name="pmid14612135" /> || 427 || 2.3 || 1,235 || NRI || Stimulant |
| [[Nisoxetine]]<ref name="pmid14612135" /> || 427 || 2.3 || 1,235 || NRI || Stimulant |
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Line 136: | Line 158: | ||
| [[Protriptyline]] || 19.6 || 1.41 || 2,100 || SNRI || TCA |
| [[Protriptyline]] || 19.6 || 1.41 || 2,100 || SNRI || TCA |
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| [[Reboxetine]]<ref name="pmid12665410">{{cite journal | vauthors = Bymaster FP, McNamara RK, Tran PV | title = New approaches to developing antidepressants by enhancing monoaminergic neurotransmission | journal = Expert Opin Investig Drugs | volume = 12 | issue = 4 | pages = 531–43 | year = 2003 | pmid = 12665410 | doi = 10.1517/13543784.12.4.531 | |
| [[Reboxetine]]<ref name="pmid12665410">{{cite journal | vauthors = Bymaster FP, McNamara RK, Tran PV | title = New approaches to developing antidepressants by enhancing monoaminergic neurotransmission | journal = Expert Opin Investig Drugs | volume = 12 | issue = 4 | pages = 531–43 | year = 2003 | pmid = 12665410 | doi = 10.1517/13543784.12.4.531 | s2cid = 20039451 }}</ref> || 129 || 1.1 || >10,000 || NRI || Stimulant |
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|- |
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| [[Sertraline]] || 0.29 || 420 || 25 || SRI || SSRI |
| [[Sertraline]] || 0.29 || 420 || 25 || SRI || SSRI |
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|- |
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| [[Sibutramine]]<ref name="pmid12119986" /> || |
| [[Sibutramine]]<ref name="pmid12119986" /> || 298–2,800 || 350–5,451 || 943–1,200 || SNDRI || SNRI |
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|- |
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| [[Trazodone]] || 160 || 8,500 || 7,400 || SRI || SARI |
| [[Trazodone]] || 160 || 8,500 || 7,400 || SRI || SARI |
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Line 150: | Line 172: | ||
| [[Venlafaxine]]*<ref name="pmid14744476" /> || 145 || 1,420 || 3,070 || SNRI || SNRI |
| [[Venlafaxine]]*<ref name="pmid14744476" /> || 145 || 1,420 || 3,070 || SNRI || SNRI |
||
|- |
|- |
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| [[Vilazodone]]*<ref name="pmid12183683">{{cite journal | vauthors = Page ME, Cryan JF, Sullivan A, Dalvi A, Saucy B, Manning DR, Lucki I | title = Behavioral and neurochemical effects of 5-(4-[4-(5-Cyano-3-indolyl)-butyl)-butyl]-1-piperazinyl)-benzofuran-2-carboxamide (EMD 68843): a combined selective inhibitor of serotonin reuptake and 5-hydroxytryptamine(1A) receptor partial agonist | journal = J. Pharmacol. Exp. Ther. | volume = 302 | issue = 3 | pages = 1220–7 | year = 2002 | pmid = 12183683 | doi = 10.1124/jpet.102.034280 | |
| [[Vilazodone]]*<ref name="pmid12183683">{{cite journal | vauthors = Page ME, Cryan JF, Sullivan A, Dalvi A, Saucy B, Manning DR, Lucki I | title = Behavioral and neurochemical effects of 5-(4-[4-(5-Cyano-3-indolyl)-butyl)-butyl]-1-piperazinyl)-benzofuran-2-carboxamide (EMD 68843): a combined selective inhibitor of serotonin reuptake and 5-hydroxytryptamine(1A) receptor partial agonist | journal = J. Pharmacol. Exp. Ther. | volume = 302 | issue = 3 | pages = 1220–7 | year = 2002 | pmid = 12183683 | doi = 10.1124/jpet.102.034280 | s2cid = 12020750 }}</ref> || 0.2 || ~60 || {{abbr|ND|No data}} || SRI || {{abbr|SMS|Serotonin modulator and stimulator}} |
||
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| [[Viloxazine]] || 17,300 || 155 || >100,000 || NRI || Stimulant |
| [[Viloxazine]] || 17,300 || 155 || >100,000 || NRI || Stimulant |
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|- |
|- |
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| [[Vortioxetine]]*<ref name="pmid21486038">{{cite journal | vauthors = Bang-Andersen B, Ruhland T, Jørgensen M, Smith G, Frederiksen K, Jensen KG, Zhong H, Nielsen SM, Hogg S, Mørk A, Stensbøl TB | title = Discovery of 1-[2-(2,4-dimethylphenylsulfanyl)phenyl]piperazine (Lu AA21004): a novel multimodal compound for the treatment of major depressive disorder | journal = J. Med. Chem. | volume = 54 | issue = 9 | pages = 3206–21 | year = 2011 | pmid = 21486038 | doi = 10.1021/jm101459g |
| [[Vortioxetine]]*<ref name="pmid21486038">{{cite journal | vauthors = Bang-Andersen B, Ruhland T, Jørgensen M, Smith G, Frederiksen K, Jensen KG, Zhong H, Nielsen SM, Hogg S, Mørk A, Stensbøl TB | title = Discovery of 1-[2-(2,4-dimethylphenylsulfanyl)phenyl]piperazine (Lu AA21004): a novel multimodal compound for the treatment of major depressive disorder | journal = J. Med. Chem. | volume = 54 | issue = 9 | pages = 3206–21 | year = 2011 | pmid = 21486038 | doi = 10.1021/jm101459g }}</ref> || 5.4 || 890 (rat) || 140 (rat) || SRI || SMS |
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| [[Zimelidine]] || 152 || 9,400 || 11,700 || SRI || SSRI |
| [[Zimelidine]] || 152 || 9,400 || 11,700 || SRI || SSRI |
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==External links== |
==External links== |
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*{{ |
*{{Commons category-inline|Monoamine reuptake inhibitors}} |
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{{Monoamine reuptake inhibitors}} |
{{Monoamine reuptake inhibitors}} |
Amonoamine reuptake inhibitor (MRI)[1] is a drug that acts as a reuptake inhibitor of one or more of the three major monoamine neurotransmitters serotonin, norepinephrine, and dopamine by blocking the action of one or more of the respective monoamine transporters (MATs), which include the serotonin transporter (SERT), norepinephrine transporter (NET), and dopamine transporter (DAT). This in turn results in an increase in the synaptic concentrations of one or more of these neurotransmitters and therefore an increase in monoaminergic neurotransmission.
The majority of currently approved antidepressants act predominantly or exclusively as MRIs, including the selective serotonin reuptake inhibitors (SSRIs), serotonin–norepinephrine reuptake inhibitors (SNRIs), and almost all of the tricyclic antidepressants (TCAs).[2] Many psychostimulants used either in the treatment of ADHDTooltip attention-deficit hyperactivity disorder or as appetite suppressants in the treatment of obesity also behave as MRIs, although notably amphetamine (and methamphetamine), which do act to some extent as monoamine reuptake inhibitors, exerts their effects primarily as releasing agents.[3][4] Additionally, psychostimulants acting as MRIs that affect dopamine such as cocaine and methylphenidate are often abusedasrecreational drugs.[5] As a result, many of them have become controlled substances, which in turn has resulted in the clandestine synthesis of a vast array of designer drugs for the purpose of bypassing drug laws; a prime example of such is the mixed monoamine reuptake inhibitor and releasing agent mephedrone.[6]
There are a variety of different kinds of MRIs, of which include the following:
Compound | SERTTooltip Serotonin transporter | NETTooltip Norepinephrine transporter | DATTooltip Dopamine transporter | Type | Class | |
---|---|---|---|---|---|---|
Amfonelic acid | ND | ND | 207 | DRI | Stimulant | |
Amineptine*[8][9] | >100,000 (rat) | 10,000 (rat) | 1,000–1,400 (rat) | DRI | Stimulant | |
Amitriptyline | 4.30 | 35 | 3,250 | SNRI | TCA | |
Amoxapine | 58 | 16.0 | 4,310 | SNRI | TeCA | |
Amphetamine | >100,000 | ND | ND | NDRA | Stimulant | |
D-Amphetamine | >100,000 | 530 | 2,900 | NDRA | Stimulant | |
L-Amphetamine | >100,000 | ND | ND | NRA | Stimulant | |
Atomoxetine | 77 | 5 | 1,451 | NRI | Stimulant | |
Bupropion | 9,100 | 52,000 | 520 | NDRI | Stimulant | |
Butriptyline | 1,360 | 5,100 | 3,940 | N/A (IA) | TCA | |
Chlorphenamine | 15.2 | 1,440 | 1,060 | SRI | Antihistamine | |
Citalopram | 1.16 | 4,070 | 28,100 | SRI | SSRI | |
Escitalopram[10] | 1.1 | 7,841 | 27,410 | SRI | SSRI | |
Clomipramine | 0.28 | 38 | 2,190 | SNRI | TCA | |
Cocaethylene[11] | 3,878 | >10,000 | 555 | SDRI | Stimulant | |
Cocaine[11] | 304 | 779 | 478 | SNDRI | Stimulant | |
Cocaine[12] | 313±17 (IC50) | 292±34 (IC50) | 211±19 (IC50) | SNDRI | Stimulant | |
Desipramine | 17.6 | 0.83 | 3,190 | SNRI | TCA | |
Desmethylcitalopram | 3.6 | 1,820 | 18,300 | SRI | SSRI | |
Desmethylsertraline | 3.0 | 390 | 129 | SRI | SSRI | |
Desmethylsibutramine[13] | 15 | 20 | 49 | SNDRI | SNRI | |
(R)-Desmethylsibutramine | 44 | 4 | 12 | SNDRI | SNRI | |
(S)-Desmethylsibutramine | 9,200 | 870 | 180 | SNDRI | SNRI | |
Desoxypipradrol[14] | 53,700 | 550 | 50 | NDRI | Stimulant | |
Desvenlafaxine*[15] | 47 | 531 | ND | SNRI | SNRI | |
Didesmethylsibutramine[13] | 20 | 15 | 45 | SNDRI | SNRI | |
(R)-Didesmethylsibutramine | 140 | 13 | 8.9 | SNDRI | SNRI | |
(S)-Didesmethylsibutramine | 4,300 | 62 | 12 | SNDRI | SNRI | |
Diphenhydramine | 3,800 | 960 | 2,200 | N/A (IA) | Antihistamine | |
Dosulepin (dothiepin) | 8.6 | 46 | 5,310 | SNRI | TCA | |
Doxepin | 68 | 29.5 | 12,100 | SNRI | TCA | |
Duloxetine*[16] | 3.7 | 20 | 439 | SNRI | SNRI | |
Etoperidone | 890 | 20,000 | 52,000 | SRI | SARI | |
Femoxetine | 11.0 | 760 | 2,050 | SRI | SSRI | |
Fluoxetine | 0.81 | 240 | 3,600 | SRI | SSRI | |
Fluvoxamine | 2.2 | 1,300 | 9,200 | SRI | SSRI | |
GBR-12935[11] | 289 | 277 | 4.90 | DRI | Stimulant | |
Hydroxybupropion[17] | ND | 1.7 (IC50) | >10 (IC50) | NDRI | Stimulant | |
Imipramine | 1.40 | 37 | 8,500 | SNRI | TCA | |
Indatraline[11] | 3.10 | 12.6 | 1.90 | SNDRI | Stimulant | |
Iprindole | 1,620 | 1,262 | 6,530 | N/A (IA) | TCA | |
Lofepramine | 70 | 5.4 | 18,000 | SNRI | TCA | |
Maprotiline | 5,800 | 11.1 | 1,000 | NRI | TeCA | |
Mazindol | 39 | 0.45 | 8.1 | NDRI | Stimulant | |
MDPVTooltip Methylenedioxypyrovalerone[18] | 3,349 | 26 | 4.1 | NDRI | Stimulant | |
Methamphetamine | >100,000 | ND | ND | NDRA | Stimulant | |
D-Methamphetamine | >100,000 | 660 | 2,800 | NDRA | Stimulant | |
L-Methamphetamine | >100,000 | ND | ND | NRA | Stimulant | |
Methylphenidate | >10,000 | 788 | 121 | NDRI | Stimulant | |
D-Methylphenidate | >10,000 | 206 | 161 | NDRI | Stimulant | |
L-Methylphenidate | >6,700 | >10,000 | 2,250 | NDRI | Stimulant | |
Mianserin | 4,000 | 71 | 9,400 | NRI | TeCA | |
Milnacipran*[16] | 151 | 68 | >100,000 | SNRI | SNRI | |
Levomilnacipran*[19] | 19.0 | 10.5 | >100,000 | SNRI | SNRI | |
Mirtazapine | >100,000 | 4,600 | >100,000 | N/A (IA) | TeCA | |
Modafinil*[20] | >50,000 | 136,000 | 4,043 | DRI | Stimulant | |
Nefazodone | 200 | 360 | 360 | SNDRI | SARI | |
Nefopam[21] | 29 | 33 | 531 | SNDRI | Analgesic | |
Nisoxetine[11] | 427 | 2.3 | 1,235 | NRI | Stimulant | |
Nomifensine | 1,010 | 15.6 | 56 | NDRI | Stimulant | |
Norfluoxetine | 1.47 | 1,426 | 420 | SRI | SSRI | |
Nortriptyline | 18 | 4.37 | 1,140 | SNRI | TCA | |
Oxaprotiline | 3,900 | 4.9 | 4,340 | NRI | TeCA | |
Paroxetine | 0.13 | 40 | 490 | SRI | SSRI | |
Protriptyline | 19.6 | 1.41 | 2,100 | SNRI | TCA | |
Reboxetine[22] | 129 | 1.1 | >10,000 | NRI | Stimulant | |
Sertraline | 0.29 | 420 | 25 | SRI | SSRI | |
Sibutramine[13] | 298–2,800 | 350–5,451 | 943–1,200 | SNDRI | SNRI | |
Trazodone | 160 | 8,500 | 7,400 | SRI | SARI | |
Trimipramine | 149 | 2,450 | 3,780 | SRI | TCA | |
Vanoxerine[11] | 73.2 | 79.2 | 4.3 | DRI | Stimulant | |
Venlafaxine*[16] | 145 | 1,420 | 3,070 | SNRI | SNRI | |
Vilazodone*[23] | 0.2 | ~60 | ND | SRI | SMS | |
Viloxazine | 17,300 | 155 | >100,000 | NRI | Stimulant | |
Vortioxetine*[24] | 5.4 | 890 (rat) | 140 (rat) | SRI | SMS | |
Zimelidine | 152 | 9,400 | 11,700 | SRI | SSRI | |
Values are Ki (nM) or, in some cases (*), IC50Tooltip half-maximal inhibitory concentration (nM). The smaller the value, the more strongly the drug binds to or inhibits the transporter. |