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.

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 as anorectics or in the treatment of ADHD also behave as MRIs.^[3] Additionally, psychostimulants acting as MRIs that affect dopamine such as cocaine and methylphenidate are often abused as recreational drugs.^[4] 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.^[5]

Types of MRIs

There are a variety of different kinds of MRIs, of which include the following:

• Selective for one monoamine transporter
  • Serotonin reuptake inhibitor (SRI)
    • See also: Selective serotonin reuptake inhibitor (SSRI)
  • Norepinephrine reuptake inhibitor (NRI)
  • Dopamine reuptake inhibitor (DRI)
• Non-selective, 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)

See also

• Monoamine releasing agent

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. Stefan Offermanns; Walter Rosenthal (2008). Encyclopedia of Molecular Pharmacology. Springer. p. 1039. ISBN 978-3-540-38916-3. Retrieved 12 May 2012.
4. 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.
5. 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.