What is a Monoamine Reuptake Inhibitor?

Introduction

A monoamine reuptake inhibitor (MRI) 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). Many psychostimulants used either in the treatment of ADHD 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. Additionally, psychostimulants acting as MRIs that affect dopamine such as cocaine and methylphenidate are often abused as recreational drugs. 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.

Types of MRIs

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

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What is a Serotonin Reuptake Inhibitor?

Introduction

A serotonin reuptake inhibitor (SRI) is a type of drug which acts as a reuptake inhibitor of the neurotransmitter serotonin (5-hydroxytryptamine, or 5-HT) 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.

Outline

A SRI is a type of monoamine reuptake inhibitor (MRI); other types of MRIs include dopamine reuptake inhibitors and norepinephrine reuptake inhibitors.

SRIs are not synonymous with selective serotonin reuptake inhibitors (SSRIs), as the latter term is usually used to describe the class of antidepressants of the same name, and because SRIs, unlike SSRIs, can either be selective or non-selective in their action. For example, cocaine, which non-selectively inhibits the reuptake of serotonin, norepinephrine, and dopamine, is a SRI but not an SSRI.

SRIs are used predominantly as antidepressants (e.g., SSRIs, SNRIs, and TCAs), though they are also commonly used in the treatment of other psychological conditions such as anxiety disorders and eating disorders. Less often, SRIs are also used to treat a variety of other medical conditions including neuropathic pain and fibromyalgia (e.g. duloxetine, milnacipran), and premature ejaculation (e.g. dapoxetine) as well as for dieting (e.g. sibutramine). Additionally, some clinically used drugs such as chlorpheniramine, dextromethorphan, and methadone possess SRI properties secondarily to their primary mechanism of action(s) and this contributes to their side effect and drug interaction profiles.

A closely related type of drug is a serotonin releasing agent (SRA), an example of which is fenfluramine.

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