A monoamine reuptake inhibitor (MRI) 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). Many psychostimulants used either in the treatment of 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. Additionally, psychostimulants acting as MRIs that affect dopamine such as cocaine and methylphenidate are often abused as recreational drugs. 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.
Types of MRIs There are a variety of different kinds of MRIs, of which include the following:
Specific for one monoamine transporter Serotonin reuptake inhibitor (SRI) Selective serotonin reuptake inhibitor (SSRI) Norepinephrine reuptake inhibitor (NRI) Selective norepinephrine reuptake inhibitor (sNRI) Dopamine reuptake inhibitor (DRI) Non-specific, binding to two or more monoamine transporters Serotonin–norepinephrine reuptake inhibitor (SNRI) Serotonin–dopamine reuptake inhibitor (SDRI) Norepinephrine–dopamine reuptake inhibitor (NDRI) Serotonin–norepinephrine–dopamine reuptake inhibitor (SNDRI)
Binding profiles
+ Binding profiles of at human Compound Type Class 3-Methylmethcathinone 4500 80270 NDRI Stimulant Amfonelic acid 207 DRI Stimulant Amineptine* >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 Amphetamine >100,000 Stimulant D-Amphetamine >100,000 530 2,900 NDRA Stimulant L-Amphetamine >100,000 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 () TCA Chlorphenamine 15.2 1,440 1,060 SRI Antihistamine Citalopram 1.16 4,070 28,100 SRI Escitalopram 1.1 7,841 27,410 SRI SSRI Clomipramine 0.28 38 2,190 SNRI TCA Cocaethylene 3,878 >10,000 555 SDRI Stimulant Cocaine 304 779 478 SNDRI Stimulant Cocaine 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 15 20 49 SNDRI SNRI (R)-Desmethylsibutramine 44 4 12 SNDRI SNRI (S)-Desmethylsibutramine 9,200 870 180 SNDRI SNRI Desoxypipradrol 53,700 550 50 NDRI Stimulant Desvenlafaxine* 47 531 SNRI SNRI Didesmethylsibutramine 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 () Antihistamine Dosulepin (dothiepin) 8.6 46 5,310 SNRI TCA Doxepin 68 29.5 12,100 SNRI TCA Duloxetine* 3.7 20 439 SNRI SNRI Etoperidone 890 20,000 52,000 SRI Eutylone 690 1,280 120 SNDRIStimulant 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 289 277 4.90 DRI Stimulant Hydroxybupropion 1.7 (IC50) >10 (IC50) NDRI Stimulant Imipramine 1.40 37 8,500 SNRI TCA Indatraline 3.10 12.6 1.90 SNDRI Stimulant Iprindole 1,620 1,262 6,530 N/A () 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 3,349 26 4.1 NDRI Stimulant Methamphetamine >100,000 NDRA Stimulant D-Methamphetamine >100,000 660 2,800 NDRA Stimulant L-Methamphetamine >100,000 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* 151 68 >100,000 SNRI SNRI Levomilnacipran* 19.0 10.5 >100,000 SNRI SNRI Mirtazapine >100,000 4,600 >100,000 N/A () TeCA Modafinil* >50,000 136,000 4,043 DRI Stimulant Nefazodone 200 360 360 SNDRI SARI Nefopam 29 33 531 SNDRI Analgesic Nisoxetine 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 129 1.1 >10,000 NRI Stimulant Sertraline 0.29 420 25 SRI SSRI Sibutramine 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 73.2 79.2 4.3 DRI Stimulant Venlafaxine* 145 1,420 3,070 SNRI SNRI Vilazodone* 0.2 ~60 SRI Viloxazine 17,300 155 >100,000 NRI Stimulant Vortioxetine* 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 (*), (nM). The smaller the value, the more strongly the drug binds to or inhibits the transporter.
See also Monoamine releasing agent
References
External links