Drug class
Amonoamine reuptake inhibitor (MRI )[ 1] drug that acts as areuptake inhibitor of one or more of the three majormonoamine neurotransmitters serotonin ,norepinephrine , anddopamine by blocking the action of one or more of the respectivemonoamine transporters (MATs), which include theserotonin transporter (SERT),norepinephrine transporter (NET), anddopamine transporter (DAT). This in turn results in an increase in thesynaptic concentrations of one or more of these neurotransmitters and therefore an increase inmonoaminergic neurotransmission .
The majority of currently approvedantidepressants act predominantly or exclusively as MRIs, including theselective serotonin reuptake inhibitors (SSRIs),serotonin–norepinephrine reuptake inhibitors (SNRIs), and almost all of thetricyclic antidepressants (TCAs).[ 2] psychostimulants used either in the treatment ofADHD Tooltip attention-deficit hyperactivity disorder or asappetite suppressants in the treatment ofobesity 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] cocaine andmethylphenidate are oftenabused asrecreational drugs .[ 5] controlled substances , which in turn has resulted in theclandestine synthesis of a vast array ofdesigner drugs for the purpose of bypassingdrug laws ; a prime example of such is the mixed monoamine reuptake inhibitor andreleasing agent mephedrone .[ 6]
There are a variety of different kinds of MRIs, of which include the following:
Specific for one monoamine transporter Non-specific, binding to two or more monoamine transporters Binding profiles ofMRIs at human MATs[ 7] Compound SERT Tooltip Serotonin transporter NET Tooltip Norepinephrine transporter DAT Tooltip Dopamine transporter Type Class 3-Methylmethcathinone 4500 80 270 NDRI Stimulant 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 Eutylone [ 17] 690 1,280 120 SNDRI Stimulant 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 [ 18] 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 MDPV Tooltip Methylenedioxypyrovalerone [ 19] 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 *[ 20] 19.0 10.5 >100,000 SNRI SNRI Mirtazapine >100,000 4,600 >100,000 N/A (IA) TeCA Modafinil *[ 21] >50,000 136,000 4,043 DRI Stimulant Nefazodone 200 360 360 SNDRI SARI Nefopam [ 22] 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 [ 23] 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 *[ 24] 0.2 ~60 ND SRI SMS Viloxazine 17,300 155 >100,000 NRI Stimulant Vortioxetine *[ 25] 5.4 890 (rat) 140 (rat) SRI SMS Zimelidine 152 9,400 11,700 SRI SSRI Values are Ki (nM) or, in some cases, when denoted by an asterisk (*),IC50 Tooltip half-maximal inhibitory concentration (nM). The smaller the value, the more strongly the drug binds to or inhibits the transporter.
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DAT Tooltip Dopamine transporter (DRIs Tooltip Dopamine reuptake inhibitors )
NET Tooltip Norepinephrine transporter (NRIs Tooltip Norepinephrine reuptake inhibitors )
Others: Antihistamines (e.g.,brompheniramine ,chlorphenamine ,pheniramine ,tripelennamine )Antipsychotics (e.g.,loxapine ,ziprasidone )Arylcyclohexylamines (e.g.,ketamine ,phencyclidine )Dopexamine Ephenidine Ginkgo biloba Indeloxazine Nefazodone Opioids (e.g.,desmetramadol ,methadone ,pethidine (meperidine) ,tapentadol ,tramadol ,levorphanol )
SERT Tooltip Serotonin transporter (SRIs Tooltip Serotonin reuptake inhibitors )
Others: A-80426 Amoxapine Antihistamines (e.g.,brompheniramine ,chlorphenamine ,dimenhydrinate ,diphenhydramine ,mepyramine (pyrilamine) ,pheniramine ,tripelennamine )Antipsychotics (e.g.,loxapine ,ziprasidone )Arylcyclohexylamines (e.g.,3-MeO-PCP ,esketamine ,ketamine ,methoxetamine ,phencyclidine )Cyclobenzaprine Delucemine Dextromethorphan Dextrorphan Efavirenz Hypidone Medifoxamine Mesembrine Mifepristone MIN-117 (WF-516) N-Me-5-HT Opioids (e.g.,dextropropoxyphene ,methadone ,pethidine (meperidine) ,levorphanol ,tapentadol ,tramadol )Roxindole
VMATs Tooltip Vesicular monoamine transporters Others
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