From Wikipedia, the free encyclopedia
Drug class
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 Tooltip 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
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:
Specific for one monoamine transporter
Non-specific, binding to two or more monoamine transporters
Binding profiles
Binding profiles of
MRIs at human
MATs
[7]
Compound
SERT Tooltip Serotonin transporter
NET Tooltip Norepinephrine transporter
DAT Tooltip 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
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 Tooltip Methylenedioxypyrovalerone
[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 Tooltip half-maximal inhibitory concentration (nM). The smaller the value, the more strongly the drug binds to or inhibits the transporter.
See also
References
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External links
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