Monoamine reuptake inhibitor

A monoamine 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.

Uses

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 ADHD 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 abused as recreational 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]

Types of MRIs

There are a variety of different kinds of MRIs, of which include the following:

Binding profiles
See also: Monoamine releasing agent § Activity profiles
Binding profiles of MRIs at human MATs[7]
CompoundSERTNETDATTypeClass
Amfonelic acidNDND207DRIStimulant
Amineptine*[8][9]>100,000 (rat)10,000 (rat)1,000–1,400 (rat)DRIStimulant
Amitriptyline4.30353,250SNRITCA
Amoxapine5816.04,310SNRITeCA
Amphetamine>100,000NDNDNDRAStimulant
  D-Amphetamine>100,0005302,900NDRAStimulant
  L-Amphetamine>100,000NDNDNRAStimulant
Atomoxetine7751,451SNRIStimulant
Bupropion9,10052,000520NDRIStimulant
Butriptyline1,3605,1003,940N/A (IA)TCA
Chlorphenamine15.21,4401,060SRIAntihistamine
Citalopram1.164,07028,100SRISSRI
  Escitalopram[10]1.17,84127,410SRISSRI
Clomipramine0.28382,190SNRITCA
Cocaethylene[11]3,878>10,000555SDRIStimulant
Cocaine[11]304779478SNDRIStimulant
Cocaine [12]313±17 (IC50)292±34 (IC50)211±19 (IC50)SNDRIStimulant
Desipramine17.60.833,190SNRITCA
Desmethylcitalopram3.61,82018,300SRISSRI
Desmethylsertraline3.0390129SRISSRI
Desmethylsibutramine[13]152049SNDRISNRI
  (R)-Desmethylsibutramine44412SNDRISNRI
  (S)-Desmethylsibutramine9,200870180SNDRISNRI
Desoxypipradrol[14]53,70055050NDRIStimulant
Desvenlafaxine*[15]47531NDSNRISNRI
Didesmethylsibutramine[13]201545SNDRISNRI
  (R)-Didesmethylsibutramine140138.9SNDRISNRI
  (S)-Didesmethylsibutramine4,3006212SNDRISNRI
Diphenhydramine3,8009602,200N/A (IA)Antihistamine
Dosulepin (dothiepin)8.6465,310SNRITCA
Doxepin6829.512,100SNRITCA
Duloxetine*[16]3.720439SNRISNRI
Etoperidone89020,00052,000SRISARI
Femoxetine11.07602,050SRISSRI
Fluoxetine0.812403,600SRISSRI
Fluvoxamine2.21,3009,200SRISSRI
GBR-12935[11]2892774.90DRIStimulant
Hydroxybupropion[17]ND1.7 (IC50)>10 (IC50)NDRIStimulant
Imipramine1.40378,500SNRITCA
Indatraline[11]3.1012.61.90SNDRIStimulant
Iprindole1,6201,2626,530N/A (IA)TCA
Lofepramine705.418,000SNRITCA
Maprotiline5,80011.11,000NRITeCA
Mazindol390.458.1NDRIStimulant
MDPV[18]3,349264.1NDRIStimulant
Methamphetamine>100,000NDNDNDRAStimulant
  D-Methamphetamine>100,0006602,800NDRAStimulant
  L-Methamphetamine>100,000NDNDNRAStimulant
Methylphenidate>10,000788121NDRIStimulant
  D-Methylphenidate>10,000206161NDRIStimulant
  L-Methylphenidate>6,700>10,0002,250NDRIStimulant
Mianserin4,000719,400NRITeCA
Milnacipran*[16]15168>100,000SNRISNRI
  Levomilnacipran*[19]19.010.5>100,000SNRISNRI
Mirtazapine>100,0004,600>100,000N/A (IA)TeCA
Modafinil*[20]>50,000136,0004,043DRIStimulant
Nefazodone200360360SNDRISARI
Nefopam[21]2933531SNDRIAnalgesic
Nisoxetine[11]4272.31,235NRIStimulant
Nomifensine1,01015.656NDRIStimulant
Norfluoxetine1.471,426420SRISSRI
Nortriptyline184.371,140SNRITCA
Oxaprotiline3,9004.94,340NRITeCA
Paroxetine0.1340490SRISSRI
Protriptyline19.61.412,100SNRITCA
Reboxetine[22]1291.1>10,000NRIStimulant
Sertraline0.2942025SRISSRI
Sibutramine[13]298–2,800350–5,451943–1,200SNDRISNRI
Trazodone1608,5007,400SRISARI
Trimipramine1492,4503,780SRITCA
Vanoxerine[11]73.279.24.3DRIStimulant
Venlafaxine*[16]1451,4203,070SNRISNRI
Vilazodone*[23]0.2~60NDSRISMS
Viloxazine17,300155>100,000NRIStimulant
Vortioxetine*[24]5.4890 (rat)140 (rat)SRISMS
Zimelidine1529,40011,700SRISSRI
Values are Ki (nM) or, in some cases (*), IC50 (nM). The smaller the value, the more strongly the
drug binds to or inhibits the transporter.

See also

References
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