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{{Short description|Drug class}} |
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A '''monoamine reuptake inhibitor''' ('''MRI''')<ref name="pmid20200509">{{cite journal |vauthors=Axel AM, Mikkelsen JD, Hansen HH | title = Tesofensine, a novel triple monoamine reuptake inhibitor, induces appetite suppression by indirect stimulation of alpha1 adrenoceptor and dopamine D1 receptor pathways in the diet-induced obese rat | journal = Neuropsychopharmacology | volume = 35 | issue = 7 | pages = 1464–76 |date=June 2010 | pmid = 20200509 | pmc = 3055463 | doi = 10.1038/npp.2010.16 }}</ref> is a [[drug]] that acts as a [[reuptake inhibitor]] of one or more of the three major [[monoamine neurotransmitter]]s [[serotonin]], [[norepinephrine]], and [[dopamine]] by blocking the action of one or more of the respective [[monoamine transporter]]s (MATs), which include the [[serotonin transporter]] (SERT), [[norepinephrine transporter]] (NET), and [[dopamine transporter]] (DAT). This in turn results in an increase in the [[synapse|synaptic]] [[concentration]]s of one or more of these neurotransmitters and therefore an increase in [[monoaminergic]] [[neurotransmission]]. |
A '''monoamine reuptake inhibitor''' ('''MRI''')<ref name="pmid20200509">{{cite journal |vauthors=Axel AM, Mikkelsen JD, Hansen HH | title = Tesofensine, a novel triple monoamine reuptake inhibitor, induces appetite suppression by indirect stimulation of alpha1 adrenoceptor and dopamine D1 receptor pathways in the diet-induced obese rat | journal = Neuropsychopharmacology | volume = 35 | issue = 7 | pages = 1464–76 |date=June 2010 | pmid = 20200509 | pmc = 3055463 | doi = 10.1038/npp.2010.16 }}</ref> is a [[drug]] that acts as a [[reuptake inhibitor]] of one or more of the three major [[monoamine neurotransmitter]]s [[serotonin]], [[norepinephrine]], and [[dopamine]] by blocking the action of one or more of the respective [[monoamine transporter]]s (MATs), which include the [[serotonin transporter]] (SERT), [[norepinephrine transporter]] (NET), and [[dopamine transporter]] (DAT). This in turn results in an increase in the [[synapse|synaptic]] [[concentration]]s of one or more of these neurotransmitters and therefore an increase in [[monoaminergic]] [[neurotransmission]]. |
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|+ Binding profiles of {{abbr|MRIs|monoamine reuptake inhibitors}} at human {{abbr|MATs|monoamine transporters}}<ref name="pmid9537821">{{cite journal | vauthors = Tatsumi M, Groshan K, Blakely RD, Richelson E | title = Pharmacological profile of antidepressants and related compounds at human monoamine transporters | journal = Eur. J. Pharmacol. | volume = 340 | issue = 2–3 | pages = 249–58 | year = 1997 | pmid = 9537821 | doi = 10.1016/s0014-2999(97)01393-9| url = https://www.academia.edu/download/45762636/s0014-2999_2897_2901393-920160518-31441-t07hp6.pdf}}</ref> |
|+ Binding profiles of {{abbr|MRIs|monoamine reuptake inhibitors}} at human {{abbr|MATs|monoamine transporters}}<ref name="pmid9537821">{{cite journal | vauthors = Tatsumi M, Groshan K, Blakely RD, Richelson E | title = Pharmacological profile of antidepressants and related compounds at human monoamine transporters | journal = Eur. J. Pharmacol. | volume = 340 | issue = 2–3 | pages = 249–58 | year = 1997 | pmid = 9537821 | doi = 10.1016/s0014-2999(97)01393-9| url = https://www.academia.edu/download/45762636/s0014-2999_2897_2901393-920160518-31441-t07hp6.pdf}}{{dead link|date=July 2022|bot=medic}}{{cbignore|bot=medic}}</ref> |
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! Compound !! {{abbrlink|SERT|Serotonin transporter}} !! {{abbrlink|NET|Norepinephrine transporter}} !! {{abbrlink|DAT|Dopamine transporter}} !! Type !! Class |
! Compound !! {{abbrlink|SERT|Serotonin transporter}} !! {{abbrlink|NET|Norepinephrine transporter}} !! {{abbrlink|DAT|Dopamine transporter}} !! Type !! Class |
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| [[Dexmethylphenidate|D-Methylphenidate]] || >10,000 || 206 || 161 || NDRI || Stimulant |
| [[Dexmethylphenidate|D-Methylphenidate]] || >10,000 || 206 || 161 || NDRI || Stimulant |
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| [[L-Methylphenidate]] || >6,700 || >10,000 || 2,250 || NDRI || Stimulant |
| [[Methylphenidate#Pharmacodynamics|L-Methylphenidate]] || >6,700 || >10,000 || 2,250 || NDRI || Stimulant |
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| [[Mianserin]] || 4,000 || 71 || 9,400 || NRI || TeCA |
| [[Mianserin]] || 4,000 || 71 || 9,400 || NRI || TeCA |
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| [[Nefazodone]] || 200 || 360 || 360 || SNDRI || SARI |
| [[Nefazodone]] || 200 || 360 || 360 || SNDRI || SARI |
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| [[Nefopam]]<ref name="pmid22711801">{{cite journal | vauthors = Gregori-Puigjané E, Setola V, Hert J, Crews BA, Irwin JJ, Lounkine E, Marnett L, Roth BL, Shoichet BK | title = Identifying mechanism-of-action targets for drugs and probes | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 109 | issue = 28 | pages = 11178–83 | year = 2012 | pmid = 22711801 | pmc = 3396511 | doi = 10.1073/pnas.1204524109 | doi-access = free }}</ref> || 29 || 33 || 531 || SNDRI || Analgesic |
| [[Nefopam]]<ref name="pmid22711801">{{cite journal | vauthors = Gregori-Puigjané E, Setola V, Hert J, Crews BA, Irwin JJ, Lounkine E, Marnett L, Roth BL, Shoichet BK | title = Identifying mechanism-of-action targets for drugs and probes | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 109 | issue = 28 | pages = 11178–83 | year = 2012 | pmid = 22711801 | pmc = 3396511 | doi = 10.1073/pnas.1204524109 | bibcode = 2012PNAS..10911178G | doi-access = free }}</ref> || 29 || 33 || 531 || SNDRI || Analgesic |
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| [[Nisoxetine]]<ref name="pmid14612135" /> || 427 || 2.3 || 1,235 || NRI || Stimulant |
| [[Nisoxetine]]<ref name="pmid14612135" /> || 427 || 2.3 || 1,235 || NRI || Stimulant |
Amonoamine 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.
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 ADHDTooltip 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 abusedasrecreational 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]
There are a variety of different kinds of MRIs, of which include the following:
Compound | SERTTooltip Serotonin transporter | NETTooltip Norepinephrine transporter | DATTooltip 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 | |
MDPVTooltip 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 (*), IC50Tooltip half-maximal inhibitory concentration (nM). The smaller the value, the more strongly the drug binds to or inhibits the transporter. |