Monoamine reuptake inhibitor: Difference between revisions

{{Short description|Drug class}}

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>

*** [[Selective serotonin reuptake inhibitor]] (SSRI)

*** [[Selective norepinephrine reuptake inhibitor]] (sNRI)

|+ 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>

| [[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

| [[Amphetamine]] || >100,000 || {{abbr|ND|No data}} || {{abbr|ND|No data}} || {{abbr|NDRA|Norepinephrine–dopamine releasing agent}} || Stimulant

|-

| &nbsp;&nbsp;[[D-Amphetamine]] || >100,000 || 530 || 2,900 || NDRA || Stimulant

|-

| &nbsp;&nbsp;[[L-Amphetamine]] || >100,000 || {{abbr|ND|No data}} || {{abbr|ND|No data}} || {{abbr|NRA|Norepinephrine releasing agent}} || Stimulant

|-

| [[Atomoxetine]] || 77 || 5 || 1,451 || NRI || Stimulant

|-

| &nbsp;&nbsp;[[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

| [[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

| [[Cocaine]]<ref>http://www.emcdda.europa.eu/system/files/publications/1814/TDAS15001ENN.pdf {{Bare URL PDF|date=March 2022}}</ref> || 313±17 (IC₅₀) || 292±34 (IC₅₀) || 211±19 (IC₅₀) || SNDRI || Stimulant

| [[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

| &nbsp;&nbsp;[[Desmethylsibutramine|(''R'')-Desmethylsibutramine]] || 44 || 4 || 12 || SNDRI || SNRI

| &nbsp;&nbsp;[[Desmethylsibutramine|(''S'')-Desmethylsibutramine]] || 9,200 || 870 || 180 || SNDRI || SNRI

| [[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

| [[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

|-

| &nbsp;&nbsp;[[Didesmethylsibutramine|(''R'')-Didesmethylsibutramine]] || 140 || 13 || 8.9 || SNDRI || SNRI

|-

| &nbsp;&nbsp;[[Didesmethylsibutramine|(''S'')-Didesmethylsibutramine]] || 4,300 || 62 || 12 || SNDRI || 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

|-

| [[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 (IC₅₀) || >10 (IC₅₀) || NDRI || Stimulant

| {{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

| [[Methamphetamine]] || >100,000 || {{abbr|ND|No data}} || {{abbr|ND|No data}} || NDRA || Stimulant

|-

| &nbsp;&nbsp;[[D-Methamphetamine]] || >100,000 || 660 || 2,800 || NDRA || Stimulant

|-

| &nbsp;&nbsp;[[Levomethamphetamine|L-Methamphetamine]] || >100,000 || {{abbr|ND|No data}} || {{abbr|ND|No data}} || NRA || Stimulant

|-

| [[Methylphenidate]] || >10,000 || 788 || 121 || NDRI || Stimulant

|-

| &nbsp;&nbsp;[[Dexmethylphenidate|D-Methylphenidate]] || >10,000 || 206 || 161 || NDRI || Stimulant

|-

| &nbsp;&nbsp;[[Methylphenidate#Pharmacodynamics|L-Methylphenidate]] || >6,700 || >10,000 || 2,250 || NDRI || Stimulant

|-

| &nbsp;&nbsp;[[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

| [[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

| [[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

| [[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

| [[Sibutramine]]<ref name="pmid12119986" /> || 298–2,800 || 350–5,451 || 943–1,200 || SNDRI || SNRI

| [[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}}

| [[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

*{{Commons category-inline|Monoamine reuptake inhibitors}}