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
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:
- Specific for one monoamine transporter
- Non-specific, binding to two or more monoamine transporters
Binding profiles
Compound | SERT | NET | DAT | 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 | |
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 | |
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[17] | 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[18] | 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*[19] | 19.0 | 10.5 | >100,000 | SNRI | SNRI | |
Mirtazapine | >100,000 | 4,600 | >100,000 | N/A (IA) | TeCA | |
Modafinil*[20] | >50,000 | 136,000 | 4,043 | DRI | Stimulant | |
Nefazodone | 200 | 360 | 360 | SNDRI | SARI | |
Nefopam[21] | 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[22] | 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*[23] | 0.2 | ~60 | ND | SRI | SMS | |
Viloxazine | 17,300 | 155 | >100,000 | NRI | Stimulant | |
Vortioxetine*[24] | 5.4 | 890 (rat) | 140 (rat) | SRI | SMS | |
Zimelidine | 152 | 9,400 | 11,700 | SRI | SSRI | |
Values are Ki (nM) or, in some cases (*), IC50 (nM). The smaller the value, the more strongly thedrug binds to or inhibits the transporter. |
See also
References
- PMID 20200509.
- ISBN 978-0-7817-7155-9. Retrieved 12 May 2012.
- PMID 20605908.
- ISBN 978-3-540-38916-3. Retrieved 12 May 2012.
- ISBN 978-1-60547-277-5. Retrieved 12 May 2012.
- PMID 21810934.
- ]
- PMID 3708219.
- S2CID 10947713.
- PMID 12232544.
- ^ PMID 14612135.
- ^ http://www.emcdda.europa.eu/system/files/publications/1814/TDAS15001ENN.pdf [bare URL PDF]
- ^ S2CID 20553857.
- PMID 23261499.
- S2CID 15063064.
- ^ S2CID 29448095.
- S2CID 1577336.
- PMID 23072836.
- PMID 23499664.
- PMID 19197004.
- PMID 22711801.
- S2CID 20039451.
- S2CID 12020750.
- PMID 21486038.
External links
- Media related to Monoamine reuptake inhibitors at Wikimedia Commons