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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 | accessdate = 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|last=Walker|first=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 |
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 | accessdate = 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|last=Walker|first=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 | accessdate = 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 | accessdate = 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== |
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 | |
Atomoxetine | 8.9 | 2.03 | 1,080 | SNRI | 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 | |
Clomipramine | 0.28 | 38 | 2,190 | SNRI | TCA | |
Cocaethylene[10] | 3,878 | >10,000 | 555 | SDRI | Stimulant | |
Cocaine[10] | 304 | 779 | 478 | 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[11] | 15 | 20 | 49 | SNDRI | SNRI | |
Desoxypipradrol[12] | 53,700 | 550 | 50 | NDRI | Stimulant | |
Desvenlafaxine*[13] | 47 | 531 | ND | SNRI | SNRI | |
Dextroamphetamine | >100,000 | 530 | 2,900 | NDRA | Stimulant | |
Dextromethamphetamine | >100,000 | 660 | 2,800 | NDRA | Stimulant | |
Didesmethylsibutramine[11] | 20 | 15 | 45 | 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*[14] | 3.7 | 20 | 439 | SNRI | SNRI | |
Escitalopram[15] | 1.1 | 7,841 | 27,410 | SRI | SSRI | |
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[10] | 289 | 277 | 4.90 | DRI | Stimulant | |
Imipramine | 1.40 | 37 | 8,500 | SNRI | TCA | |
Indatraline[10] | 3.10 | 12.6 | 1.90 | SNDRI | Stimulant | |
Iprindole | 1,620 | 1,262 | 6,530 | N/A (IA) | TCA | |
Levomilnacipran*[16] | 19.0 | 10.5 | >100,000 | SNRI | SNRI | |
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[17] | 3,349 | 26 | 4.1 | NDRI | Stimulant | |
Methylphenidate | 44,000 | 234 | 24 | NDRI | Stimulant | |
Mianserin | 4,000 | 71 | 9,400 | NRI | TeCA | |
Milnacipran*[14] | 151 | 68 | >100,000 | SNRI | SNRI | |
Mirtazapine | >100,000 | 4,600 | >100,000 | N/A (IA) | TeCA | |
Modafinil*[18] | >50,000 | 136,000 | 4,043 | DRI | Stimulant | |
Nefazodone | 200 | 360 | 360 | SNDRI | SARI | |
Nefopam[19] | 29 | 33 | 531 | SNDRI | Analgesic | |
Nisoxetine[10] | 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[20] | 129 | 1.1 | >10,000 | NRI | Stimulant | |
Sertraline | 0.29 | 420 | 25 | SRI | SSRI | |
Sibutramine[11] | 298 | 5,451 | 943 | SNDRI | SNRI | |
Trazodone | 160 | 8,500 | 7,400 | SRI | SARI | |
Trimipramine | 149 | 2,450 | 3,780 | SRI | TCA | |
Vanoxerine[10] | 73.2 | 79.2 | 4.3 | DRI | Stimulant | |
Venlafaxine*[14] | 145 | 1,420 | 3,070 | SNRI | SNRI | |
Vilazodone*[21] | 0.2 | ~60 | ND | SRI | SMS | |
Viloxazine | 17,300 | 155 | >100,000 | NRI | Stimulant | |
Vortioxetine*[22] | 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. |