Monoamine reuptake inhibitor

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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.

Contents

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:

Binding profiles

See also

Related Research Articles

<span class="mw-page-title-main">Monoamine transporter</span> Proteins that function as integral plasma-membrane transporters

Monoamine transporters (MATs) are proteins that function as integral plasma-membrane transporters to regulate concentrations of extracellular monoamine neurotransmitters. The three major classes are serotonin transporters (SERTs), dopamine transporters (DATs), and norepinephrine transporters (NETs) and are responsible for the reuptake of their associated amine neurotransmitters. MATs are located just outside the synaptic cleft (peri-synaptically), transporting monoamine transmitter overflow from the synaptic cleft back to the cytoplasm of the pre-synaptic neuron. MAT regulation generally occurs through protein phosphorylation and post-translational modification. Due to their significance in neuronal signaling, MATs are commonly associated with drugs used to treat mental disorders as well as recreational drugs. Compounds targeting MATs range from medications such as the wide variety of tricyclic antidepressants, selective serotonin reuptake inhibitors such as fluoxetine (Prozac) to stimulant medications such as methylphenidate (Ritalin) and amphetamine in its many forms and derivatives methamphetamine (Desoxyn) and lisdexamfetamine (Vyvanse). Furthermore, drugs such as MDMA and natural alkaloids such as cocaine exert their effects in part by their interaction with MATs, by blocking the transporters from mopping up dopamine, serotonin, and other neurotransmitters from the synapse.

<span class="mw-page-title-main">Serotonin–norepinephrine reuptake inhibitor</span> Class of antidepressant medication

Serotonin–norepinephrine reuptake inhibitors (SNRIs) are a class of antidepressant medications used to treat major depressive disorder (MDD), anxiety disorders, social phobia, chronic neuropathic pain, fibromyalgia syndrome (FMS), and menopausal symptoms. Off-label uses include treatments for attention-deficit hyperactivity disorder (ADHD), and obsessive–compulsive disorder (OCD). SNRIs are monoamine reuptake inhibitors; specifically, they inhibit the reuptake of serotonin and norepinephrine. These neurotransmitters are thought to play an important role in mood regulation. SNRIs can be contrasted with the selective serotonin reuptake inhibitors (SSRIs) and norepinephrine reuptake inhibitors (NRIs), which act upon single neurotransmitters.

<span class="mw-page-title-main">Norepinephrine reuptake inhibitor</span> Class of drug

A norepinephrine reuptake inhibitor or noradrenaline reuptake inhibitor or adrenergic reuptake inhibitor (ARI), is a type of drug that acts as a reuptake inhibitor for the neurotransmitters norepinephrine (noradrenaline) and epinephrine (adrenaline) by blocking the action of the norepinephrine transporter (NET). This in turn leads to increased extracellular concentrations of norepinephrine and epinephrine and therefore can increase adrenergic neurotransmission.

A serotonin–norepinephrine–dopamine reuptake inhibitor (SNDRI), also known as a triple reuptake inhibitor (TRI), is a type of drug that acts as a combined reuptake inhibitor of the monoamine neurotransmitters serotonin, norepinephrine, and dopamine. It does this by concomitantly inhibiting the serotonin transporter (SERT), norepinephrine transporter (NET), and dopamine transporter (DAT), respectively. Inhibition of the reuptake of these neurotransmitters increases their extracellular concentrations and, therefore, results in an increase in serotonergic, adrenergic, and dopaminergic neurotransmission. The naturally-occurring and potent SNDRI cocaine is widely used recreationally and often illegally for the euphoric effects it produces.

<span class="mw-page-title-main">Etilamfetamine</span> Chemical compound

Etilamfetamine, also known as N-ethylamphetamine and formerly sold under the brand names Apetinil and Adiparthrol, is a stimulant drug of the amphetamine family. It was invented in the early 20th century and was subsequently used as an anorectic or appetite suppressant in the 1950s, but was not as commonly used as other amphetamines such as amphetamine, methamphetamine, and benzphetamine, and was largely discontinued once newer drugs such as phenmetrazine were introduced.

<span class="mw-page-title-main">Naphthylaminopropane</span> Chemical compound

Naphthylaminopropane, also known as naphthylisopropylamine (NIPA), is an experimental drug of the amphetamine and naphthylaminopropane families that was under investigation for the treatment of alcohol and stimulant addiction.

<span class="mw-page-title-main">Serotonin reuptake inhibitor</span> Class of drug

A serotonin reuptake inhibitor (SRI) is a type of drug which acts as a reuptake inhibitor of the neurotransmitter serotonin by blocking the action of the serotonin transporter (SERT). This in turn leads to increased extracellular concentrations of serotonin and, therefore, an increase in serotonergic neurotransmission. It is a type of monoamine reuptake inhibitor (MRI); other types of MRIs include dopamine reuptake inhibitors and norepinephrine reuptake inhibitors.

<span class="mw-page-title-main">Norfenfluramine</span> Never-marketed drug of the amphetamine family

Norfenfluramine, or 3-trifluoromethylamphetamine, is a never-marketed drug of the amphetamine family and a major active metabolite of the appetite suppressants fenfluramine and benfluorex. The compound is a racemic mixture of two enantiomers with differing activities, dexnorfenfluramine and levonorfenfluramine.

<span class="mw-page-title-main">Reuptake inhibitor</span> Type of drug

Reuptake inhibitors (RIs) are a type of reuptake modulators. It is a drug that inhibits the plasmalemmal transporter-mediated reuptake of a neurotransmitter from the synapse into the pre-synaptic neuron. This leads to an increase in extracellular concentrations of the neurotransmitter and an increase in neurotransmission. Various drugs exert their psychological and physiological effects through reuptake inhibition, including many antidepressants and psychostimulants.

<span class="mw-page-title-main">Monoamine releasing agent</span> Class of compounds

A monoamine releasing agent (MRA), or simply monoamine releaser, is a drug that induces the release of one or more monoamine neurotransmitters from the presynaptic neuron into the synapse, leading to an increase in the extracellular concentrations of the neurotransmitters and hence enhanced signaling by those neurotransmitters. The monoamine neurotransmitters include serotonin, norepinephrine, and dopamine; MRAs can induce the release of one or more of these neurotransmitters.

<span class="mw-page-title-main">Norepinephrine releasing agent</span> Catecholaminergic type of drug

A norepinephrine releasing agent (NRA), also known as an adrenergic releasing agent, is a catecholaminergic type of drug that induces the release of norepinephrine (noradrenaline) and epinephrine (adrenaline) from the pre-synaptic neuron into the synapse. This in turn leads to increased extracellular concentrations of norepinephrine and epinephrine therefore an increase in adrenergic neurotransmission.

<span class="mw-page-title-main">Dopamine releasing agent</span> Type of drug

A dopamine releasing agent (DRA) is a type of drug which induces the release of dopamine in the body and/or brain.

<span class="mw-page-title-main">Norepinephrine–dopamine reuptake inhibitor</span> Drug that inhibits the reuptake of norepinephrine and dopamine

A norepinephrine–dopamine reuptake inhibitor (NDRI) is a type of drug that inhibits the reuptake of the monoamine neurotransmitters norepinephrine and dopamine and thereby increases extracellular levels of these neurotransmitters and noradrenergic and dopaminergic neurotransmission. They work by competitively and/or noncompetitively inhibiting the norepinephrine transporter (NET) and dopamine transporter (DAT).

<span class="mw-page-title-main">4-Methylamphetamine</span> Stimulant and anorectic drug of the amphetamine class

4-Methylamphetamine (4-MA), also known by the former proposed brand name Aptrol, is a stimulant and anorectic drug of the amphetamine family. It is structurally related to mephedrone (4-methylmethcathinone).

<span class="mw-page-title-main">4-Methylmethamphetamine</span> Stimulant and entactogen drug of the amphetamine class

4-Methylmethamphetamine (4-MMA), also known as mephedrine, is a putative stimulant and entactogen drug of the amphetamine family. It acts as a serotonin–norepinephrine–dopamine releasing agent (SNDRA). The drug is the β-deketo analogue of mephedrone and the N-methyl analogue of 4-methylamphetamine (4-MA).

<span class="mw-page-title-main">Serotonin–dopamine reuptake inhibitor</span> Class of drug

A serotonin–dopamine reuptake inhibitor (SDRI) is a type of drug which acts as a reuptake inhibitor of the monoamine neurotransmitters serotonin and dopamine by blocking the actions of the serotonin transporter (SERT) and dopamine transporter (DAT), respectively. This in turn leads to increased extracellular concentrations of serotonin and dopamine, and, therefore, an increase in serotonergic and dopaminergic neurotransmission.

<span class="mw-page-title-main">Pseudophenmetrazine</span> Chemical compound

Pseudophenmetrazine is a psychostimulant of the phenylmorpholine group. It is the N-demethylated and cis-configured analogue of phendimetrazine as well as the cis-configured stereoisomer of phenmetrazine. In addition, along with phenmetrazine, it is believed to be one of the active metabolites of phendimetrazine, which itself is inactive and behaves merely as a prodrug.

<span class="mw-page-title-main">Methamnetamine</span> Chemical compound

Methamnetamine is a triple monoamine releasing agent of the amphetamine and naphthylaminopropane families. It is the N-methyl analog of the non-neurotoxic experimental drug naphthylaminopropane and the naphthalene analog of methamphetamine. It has been sold online as a designer drug.

<span class="mw-page-title-main">Naphthylmetrazine</span> Pharmaceutical compound

Naphthylmetrazine, also known as 3-methyl-2-(2′-naphthyl)morpholine, is a monoamine releasing agent (MRA) and monoamine reuptake inhibitor (MRI) of the phenylmorpholine and naphthylaminopropane families related to phenmetrazine. It is a analogue of phenmetrazine in which the phenyl ring has been replaced with a naphthalene ring.

<span class="mw-page-title-main">Substituted naphthylethylamine</span>

The substituted naphthylethylamines are a class of chemical compounds based on naphthalene. Many naphthylethylamines are naphthylaminopropanes due to the presence of a methyl group at the alpha carbon of the alkyl chain. The naphthylethylamines are derivatives of the phenethylamines, while the naphthylaminopropanes are derivatives of the amphetamines.

References

  1. ↑ Axel AM, Mikkelsen JD, Hansen HH (June 2010). "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". Neuropsychopharmacology. 35 (7): 1464–76. doi:10.1038/npp.2010.16. PMC   3055463 . PMID   20200509.
  2. ↑ Richard Finkel; Michelle Alexia Clark; Pamela C. Champe; Luigi X. Cubeddu (16 July 2008). Lippincott's Illustrated Reviews: Pharmacology. Lippincott Williams & Wilkins. p. 141. ISBN   978-0-7817-7155-9 . Retrieved 12 May 2012.
  3. ↑ Walker, Q. David; Morris, Sarah E.; Arrant, Andrew E.; Nagel, Jacqueline M.; Parylak, Sarah; Zhou, Guiying; Caster, Joseph M.; Kuhn, Cynthia M. (October 2010). "Dopamine Uptake Inhibitors but Not Dopamine Releasers Induce Greater Increases in Motor Behavior and Extracellular Dopamine in Adolescent Rats Than in Adult Male Rats". The Journal of Pharmacology and Experimental Therapeutics. 335 (1): 124–132. doi:10.1124/jpet.110.167320. ISSN   0022-3565. PMC   2957786 . PMID   20605908.
  4. ↑ Stefan Offermanns; Walter Rosenthal (2008). Encyclopedia of Molecular Pharmacology. Springer. p. 1039. ISBN   978-3-540-38916-3 . Retrieved 12 May 2012.
  5. ↑ Pedro Ruiz; Eric C. Strain (15 April 2011). Lowinson and Ruiz's Substance Abuse: A Comprehensive Textbook. Lippincott Williams & Wilkins. p. 55. ISBN   978-1-60547-277-5 . Retrieved 12 May 2012.
  6. ↑ Hadlock GC, Webb KM, McFadden LM, et al. (November 2011). "4-Methylmethcathinone (mephedrone): neuropharmacological effects of a designer stimulant of abuse". The Journal of Pharmacology and Experimental Therapeutics. 339 (2): 530–6. doi:10.1124/jpet.111.184119. PMC   3200001 . PMID   21810934.
  7. ↑ Tatsumi M, Groshan K, Blakely RD, Richelson E (1997). "Pharmacological profile of antidepressants and related compounds at human monoamine transporters" (PDF). Eur. J. Pharmacol. 340 (2–3): 249–58. doi:10.1016/s0014-2999(97)01393-9. PMID   9537821.[ dead link ]
  8. ↑ Ceci A, Garattini S, Gobbi M, Mennini T (1986). "Effect of long term amineptine treatment on pre- and postsynaptic mechanisms in rat brain". Br. J. Pharmacol. 88 (1): 269–75. doi:10.1111/j.1476-5381.1986.tb09495.x. PMC   1917102 . PMID   3708219.
  9. ↑ Garattini S, Mennini T (1989). "Pharmacology of amineptine: synthesis and updating". Clin Neuropharmacol. 12 Suppl 2: S13–8. doi:10.1097/00002826-198912002-00003. PMID   2698268. S2CID   10947713.
  10. ↑ Owens JM, Knight DL, Nemeroff CB (2002). "[Second generation SSRIS: human monoamine transporter binding profile of escitalopram and R-fluoxetine]". Encephale (in French). 28 (4): 350–5. PMID   12232544.
  11. 1 2 3 4 5 6 Rothman RB, Baumann MH (2003). "Monoamine transporters and psychostimulant drugs". Eur. J. Pharmacol. 479 (1–3): 23–40. doi:10.1016/j.ejphar.2003.08.054. PMID   14612135.
  12. ↑ "EMCDDA–Europol Joint Report on a new psychoactive substance: 1-phenyl-2-(1-pyrrolidinyl)-1-pentanone (α-PVP)". www.euda.europa.eu. Retrieved 2024-07-16.
  13. 1 2 3 Nisoli E, Carruba MO (2000). "An assessment of the safety and efficacy of sibutramine, an anti-obesity drug with a novel mechanism of action". Obes Rev. 1 (2): 127–39. doi:10.1046/j.1467-789x.2000.00020.x. PMID   12119986. S2CID   20553857.
  14. ↑ Iversen L, Gibbons S, Treble R, Setola V, Huang XP, Roth BL (2013). "Neurochemical profiles of some novel psychoactive substances". Eur. J. Pharmacol. 700 (1–3): 147–51. doi:10.1016/j.ejphar.2012.12.006. PMC   3582025 . PMID   23261499.
  15. ↑ Deecher DC, Beyer CE, Johnston G, Bray J, Shah S, Abou-Gharbia M, Andree TH (2006). "Desvenlafaxine succinate: A new serotonin and norepinephrine reuptake inhibitor". J. Pharmacol. Exp. Ther. 318 (2): 657–65. doi:10.1124/jpet.106.103382. PMID   16675639. S2CID   15063064.
  16. 1 2 3 Vaishnavi SN, Nemeroff CB, Plott SJ, Rao SG, Kranzler J, Owens MJ (2004). "Milnacipran: a comparative analysis of human monoamine uptake and transporter binding affinity". Biol. Psychiatry. 55 (3): 320–2. doi:10.1016/j.biopsych.2003.07.006. PMID   14744476. S2CID   29448095.
  17. ↑ Glatfelter GC, Walther D, Evans-Brown M, Baumann MH (April 2021). "Eutylone and Its Structural Isomers Interact with Monoamine Transporters and Induce Locomotor Stimulation". ACS Chem Neurosci. 12 (7): 1172. doi:10.1021/acschemneuro.0c00797. PMC   9423000 . PMID   33689284.
  18. ↑ Damaj, MI; Carroll, FI; Eaton, JB; Navarro, HA; Blough, BE; Mirza, S; Lukas, RJ; Martin, BR (September 2004). "Enantioselective effects of hydroxy metabolites of bupropion on behavior and on function of monoamine transporters and nicotinic receptors". Molecular Pharmacology. 66 (3): 675–82. doi:10.1124/mol.104.001313. PMID   15322260. S2CID   1577336.
  19. ↑ Baumann MH, Partilla JS, Lehner KR, Thorndike EB, Hoffman AF, Holy M, Rothman RB, Goldberg SR, Lupica CR, Sitte HH, Brandt SD, Tella SR, Cozzi NV, Schindler CW (2013). "Powerful cocaine-like actions of 3,4-methylenedioxypyrovalerone (MDPV), a principal constituent of psychoactive 'bath salts' products". Neuropsychopharmacology. 38 (4): 552–62. doi:10.1038/npp.2012.204. PMC   3572453 . PMID   23072836.
  20. ↑ Auclair AL, Martel JC, Assié MB, Bardin L, Heusler P, Cussac D, Marien M, Newman-Tancredi A, O'Connor JA, Depoortère R (2013). "Levomilnacipran (F2695), a norepinephrine-preferring SNRI: profile in vitro and in models of depression and anxiety". Neuropharmacology. 70: 338–47. doi: 10.1016/j.neuropharm.2013.02.024 . PMID   23499664.
  21. ↑ Zolkowska D, Jain R, Rothman RB, Partilla JS, Roth BL, Setola V, Prisinzano TE, Baumann MH (2009). "Evidence for the involvement of dopamine transporters in behavioral stimulant effects of modafinil". J. Pharmacol. Exp. Ther. 329 (2): 738–46. doi:10.1124/jpet.108.146142. PMC   2672878 . PMID   19197004.
  22. ↑ Gregori-Puigjané E, Setola V, Hert J, Crews BA, Irwin JJ, Lounkine E, Marnett L, Roth BL, Shoichet BK (2012). "Identifying mechanism-of-action targets for drugs and probes". Proc. Natl. Acad. Sci. U.S.A. 109 (28): 11178–83. Bibcode:2012PNAS..10911178G. doi: 10.1073/pnas.1204524109 . PMC   3396511 . PMID   22711801.
  23. ↑ Bymaster FP, McNamara RK, Tran PV (2003). "New approaches to developing antidepressants by enhancing monoaminergic neurotransmission". Expert Opin Investig Drugs. 12 (4): 531–43. doi:10.1517/13543784.12.4.531. PMID   12665410. S2CID   20039451.
  24. ↑ Page ME, Cryan JF, Sullivan A, Dalvi A, Saucy B, Manning DR, Lucki I (2002). "Behavioral and neurochemical effects of 5-(4-[4-(5-Cyano-3-indolyl)-butyl)-butyl]-1-piperazinyl)-benzofuran-2-carboxamide (EMD 68843): a combined selective inhibitor of serotonin reuptake and 5-hydroxytryptamine(1A) receptor partial agonist". J. Pharmacol. Exp. Ther. 302 (3): 1220–7. doi:10.1124/jpet.102.034280. PMID   12183683. S2CID   12020750.
  25. ↑ Bang-Andersen B, Ruhland T, Jørgensen M, Smith G, Frederiksen K, Jensen KG, Zhong H, Nielsen SM, Hogg S, Mørk A, Stensbøl TB (2011). "Discovery of 1-[2-(2,4-dimethylphenylsulfanyl)phenyl]piperazine (Lu AA21004): a novel multimodal compound for the treatment of major depressive disorder". J. Med. Chem. 54 (9): 3206–21. doi:10.1021/jm101459g. PMID   21486038.
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