Dopamine reuptake inhibitor - AbsoluteAstronomy.com

A dopamine reuptake inhibitor (DRI, DARI) is a type of drug

Drug

A drug, broadly speaking, is any substance that, when absorbed into the body of a living organism, alters normal bodily function. There is no single, precise definition, as there are different meanings in drug control law, government regulations, medicine, and colloquial usage.In pharmacology, a...

that acts as a reuptake inhibitor

Reuptake inhibitor

A reuptake inhibitor , also known as a transporter blocker, is a drug that inhibits the plasmalemmal transporter-mediated reuptake of a neurotransmitter from the synapse into the pre-synaptic neuron, leading to an increase in the extracellular concentrations of the neurotransmitter and therefore an...

for the neurotransmitter

Neurotransmitter

Neurotransmitters are endogenous chemicals that transmit signals from a neuron to a target cell across a synapse. Neurotransmitters are packaged into synaptic vesicles clustered beneath the membrane on the presynaptic side of a synapse, and are released into the synaptic cleft, where they bind to...

dopamine

Dopamine

Dopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this substituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D1, D2, D3, D4, and D5—and their...

by blocking the action

Drug action

The action of drugs on the human body is called pharmacodynamics, and what the body does with the drug is called pharmacokinetics. The drugs that enter the human tend to stimulate certain receptors, ion channels, act on enzymes or transporter proteins...

of the dopamine transporter

Dopamine transporter

The dopamine transporter is a membrane-spanning protein that pumps the neurotransmitter dopamine out of the synapse back into cytosol, from which other transporters sequester DA and NE into vesicles for later storage and release...

(DAT). This in turn leads to increased extracellular

Extracellular

In cell biology, molecular biology and related fields, the word extracellular means "outside the cell". This space is usually taken to be outside the plasma membranes, and occupied by fluid...

concentration

Concentration

In chemistry, concentration is defined as the abundance of a constituent divided by the total volume of a mixture. Four types can be distinguished: mass concentration, molar concentration, number concentration, and volume concentration...

s of dopamine and therefore an increase in dopaminergic

Dopaminergic

Dopaminergic means related to the neurotransmitter dopamine. For example, certain proteins such as the dopamine transporter , vesicular monoamine transporter 2 , and dopamine receptors can be classified as dopaminergic, and neurons which synthesize or contain dopamine and synapses with dopamine...

neurotransmission

Neurotransmission

Neurotransmission , also called synaptic transmission, is the process by which signaling molecules called neurotransmitters are released by a neuron , and bind to and activate the receptors of another neuron...

Indications

DRIs may be used in the clinical treatment of attention-deficit hyperactivity disorder

Attention-deficit hyperactivity disorder

Attention deficit hyperactivity disorder is a developmental disorder. It is primarily characterized by "the co-existence of attentional problems and hyperactivity, with each behavior occurring infrequently alone" and symptoms starting before seven years of age.ADHD is the most commonly studied and...

(ADHD), narcolepsy

Narcolepsy

Narcolepsy is a chronic sleep disorder, or dyssomnia, characterized by excessive sleepiness and sleep attacks at inappropriate times, such as while at work. People with narcolepsy often experience disturbed nocturnal sleep and an abnormal daytime sleep pattern, which often is confused with insomnia...

, and fatigue or lethargy as stimulant

Stimulant

Stimulants are psychoactive drugs which induce temporary improvements in either mental or physical function or both. Examples of these kinds of effects may include enhanced alertness, wakefulness, and locomotion, among others...

s, obesity

Obesity

Obesity is a medical condition in which excess body fat has accumulated to the extent that it may have an adverse effect on health, leading to reduced life expectancy and/or increased health problems...

as anorectic

Anorectic

An anorectic or anorexic , also known as anorexigenic or appetite suppressant, is a dietary supplement and/or drug which reduces appetite, food consumption, and as a result, causes weight loss to occur.-List of anorectics:Numerous pharmaceutical compounds are marketed as appetite suppressants.The...

s or appetite suppressants for weight loss

Weight loss

Weight loss, in the context of medicine, health or physical fitness, is a reduction of the total body mass, due to a mean loss of fluid, body fat or adipose tissue and/or lean mass, namely bone mineral deposits, muscle, tendon and other connective tissue...

purposes, as well as mood disorder

Mood disorder

Mood disorder is the term designating a group of diagnoses in the Diagnostic and Statistical Manual of Mental Disorders classification system where a disturbance in the person's mood is hypothesized to be the main underlying feature...

s such as major depressive disorder (MDD) usually of the treatment-resistant or atypical

Atypical depression

Atypical depression is a subtype of dysthymia and major depression, sharing many of the symptoms of both, but also being characterized by mood reactivity—being able to experience improved mood in response to positive events. In contrast, sufferers of "melancholic" depression generally cannot...

variants as antidepressant

Antidepressant

An antidepressant is a psychiatric medication used to alleviate mood disorders, such as major depression and dysthymia and anxiety disorders such as social anxiety disorder. According to Gelder, Mayou &*Geddes people with a depressive illness will experience a therapeutic effect to their mood;...

s, social phobia (SP) also known as social anxiety disorder

Social anxiety disorder

Social anxiety disorder , also known as social phobia, is an anxiety disorder characterized by intense fear in social situations causing considerable distress and impaired ability to function in at least some parts of daily life...

(SAD), and perhaps other anxiety disorder

Anxiety disorder

Anxiety disorder is a blanket term covering several different forms of abnormal and pathological fear and anxiety. Conditions now considered anxiety disorders only came under the aegis of psychiatry at the end of the 19th century. Gelder, Mayou & Geddes explains that anxiety disorders are...

s as anxiolytic

Anxiolytic

An anxiolytic is a drug used for the treatment of anxiety, and its related psychological and physical symptoms...

s, parkinsonism

Parkinsonism

Parkinsonism is a neurological syndrome characterized by tremor, hypokinesia, rigidity, and postural instability. The underlying causes of parkinsonism are numerous, and diagnosis can be complex...

such as that seen in Parkinson's disease

Parkinson's disease

Parkinson's disease is a degenerative disorder of the central nervous system...

as antiparkinsonian agents, for palliative care of cancer related lethargy, drug addiction and/or dependence

Physical dependence

Physical dependence refers to a state resulting from chronic use of a drug that has produced tolerance and where negative physical symptoms of withdrawal result from abrupt discontinuation or dosage reduction...

as anticraving agents, and both as augmentation

Augmentation (psychiatry)

Augmentation is the combination of two or more drugs to achieve better treatment results....

s and to offset some of the side effects of other drugs like the selective serotonin reuptake inhibitor

Selective serotonin reuptake inhibitor

Selective serotonin re-uptake inhibitors or serotonin-specific reuptake inhibitor are a class of compounds typically used as antidepressants in the treatment of depression, anxiety disorders, and some personality disorders. The efficacy of SSRIs is disputed...

s (SSRIs), such as sexual dysfunction

Sexual dysfunction

Sexual dysfunction or sexual malfunction refers to a difficulty experienced by an individual or a couple during any stage of a normal sexual activity, including desire, arousal or orgasm....

General

DRIs can induce a wide range of psychological and physiological effects, including the following:
It should be noted, however, that many of these properties are dependent on whether the DRI in question is capable of crossing the blood-brain-barrier (BBB). Those that do not will only produce peripheral

Peripheral

A peripheral is a device attached to a host computer, but not part of it, and is more or less dependent on the host. It expands the host's capabilities, but does not form part of the core computer architecture....

effects.

Overdose

At very high doses and/or with chronic administration characterized by overdose, stimulant psychosis may develop, the symptom

Symptom

A symptom is a departure from normal function or feeling which is noticed by a patient, indicating the presence of disease or abnormality...

s of which can include the following:
Additionally, potential incarceration

Incarceration

Incarceration is the detention of a person in prison, typically as punishment for a crime .People are most commonly incarcerated upon suspicion or conviction of committing a crime, and different jurisdictions have differing laws governing the function of incarceration within a larger system of...

, hospitalization, institutionalization

Psychiatric hospital

Psychiatric hospitals, also known as mental hospitals, are hospitals specializing in the treatment of serious mental disorders. Psychiatric hospitals vary widely in their size and grading. Some hospitals may specialise only in short-term or outpatient therapy for low-risk patients...

, and/or death

Death

Death is the permanent termination of the biological functions that sustain a living organism. Phenomena which commonly bring about death include old age, predation, malnutrition, disease, and accidents or trauma resulting in terminal injury....

, on account of extreme erratic

Recklessness (psychology)

Recklessness is disregard for or indifference to the dangers of a situation or for the consequences of one's actions....

behavior

Behavior

Behavior or behaviour refers to the actions and mannerisms made by organisms, systems, or artificial entities in conjunction with its environment, which includes the other systems or organisms around as well as the physical environment...

which may include acts of crime

Crime

Crime is the breach of rules or laws for which some governing authority can ultimately prescribe a conviction...

, assault

Assault

In law, assault is a crime causing a victim to fear violence. The term is often confused with battery, which involves physical contact. The specific meaning of assault varies between countries, but can refer to an act that causes another to apprehend immediate and personal violence, or in the more...

, accidental or intentional self-injury, and/or suicide

Suicide

Suicide is the act of intentionally causing one's own death. Suicide is often committed out of despair or attributed to some underlying mental disorder, such as depression, bipolar disorder, schizophrenia, alcoholism, or drug abuse...

, as well as illicit

Prohibition (drugs)

The prohibition of drugs through sumptuary legislation or religious law is a common means of attempting to prevent drug use. Prohibition of drugs has existed at various levels of government or other authority from the Middle Ages to the present....

drug abuse

Drug abuse

Substance abuse, also known as drug abuse, refers to a maladaptive pattern of use of a substance that is not considered dependent. The term "drug abuse" does not exclude dependency, but is otherwise used in a similar manner in nonmedical contexts...

, may ensue under such circumstances.

Abuse

Due to their strong rewarding

Reward system

In neuroscience, the reward system is a collection of brain structures which attempts to regulate and control behavior by inducing pleasurable effects...

and reinforcing

Reinforcement

Reinforcement is a term in operant conditioning and behavior analysis for the process of increasing the rate or probability of a behavior in the form of a "response" by the delivery or emergence of a stimulus Reinforcement is a term in operant conditioning and behavior analysis for the process of...

properties, DRIs are notorious for their high abuse potential

Drug abuse

and liability to cause craving

Craving (withdrawal)

When going through withdrawal, craving is a psychological urge to administer a discontinued medication or recreational drug.-Duration:The duration that cravings last after discontinuation varies substantially between different addictive drugs...

s, addiction, and dependence

Physical dependence

. DRIs such as cocaine

Cocaine

Cocaine is a crystalline tropane alkaloid that is obtained from the leaves of the coca plant. The name comes from "coca" in addition to the alkaloid suffix -ine, forming cocaine. It is a stimulant of the central nervous system, an appetite suppressant, and a topical anesthetic...

, methylphenidate

Methylphenidate

Methylphenidate is a psychostimulant drug approved for treatment of attention-deficit hyperactivity disorder, postural orthostatic tachycardia syndrome and narcolepsy. It may also be prescribed for off-label use in treatment-resistant cases of lethargy, depression, neural insult and obesity...

, and some tricyclic antidepressants, combination releasing agent

Releasing agent

A releasing agent , or simply releaser, is a drug that induces the release of a neurotransmitter from the presynaptic neuron into the synapse, leading to an increase in the extracellular concentrations of the neurotransmitter. Many drugs use neurotransmitter release to exert their psychological and...

s such as amphetamine

Amphetamine

Amphetamine or amfetamine is a psychostimulant drug of the phenethylamine class which produces increased wakefulness and focus in association with decreased fatigue and appetite.Brand names of medications that contain, or metabolize into, amphetamine include Adderall, Dexedrine, Dextrostat,...

, cocaine

Cocaine

, methamphetamine

Methamphetamine

Methamphetamine is a psychostimulant of the phenethylamine and amphetamine class of psychoactive drugs...

, and MDMA

Methylenedioxymethamphetamine

MDMA is an entactogenic drug of the phenethylamine and amphetamine class of drugs. In popular culture, MDMA has become widely known as "ecstasy" , usually referring to its street pill form, although this term may also include the presence of possible adulterants...

("ecstasy") are widely abused

Recreational drug use

Recreational drug use is the use of a drug, usually psychoactive, with the intention of creating or enhancing recreational experience. Such use is controversial, however, often being considered to be also drug abuse, and it is often illegal...

throughout the world

World

World is a common name for the whole of human civilization, specifically human experience, history, or the human condition in general, worldwide, i.e. anywhere on Earth....

. It is estimated that there are approximately six million people addicted to cocaine in the United States

United States

The United States of America is a federal constitutional republic comprising fifty states and a federal district...

(U.S.) alone.

Notably, some DRIs have a lower abuse potential than others. Those that have a slow onset

Absorption (Pharmacokinetics)

In pharmacology , absorption is the movement of a drug into the bloodstream.Absorption involves several phases...

and long duration

Biological half-life

The biological half-life or elimination half-life of a substance is the time it takes for a substance to lose half of its pharmacologic, physiologic, or radiologic activity, as per the MeSH definition...

of action

Drug action

such as bupropion

Bupropion

Bupropion is an atypical antidepressant and smoking cessation aid. The drug is a non-tricyclic antidepressant and differs from most commonly prescribed antidepressants such as SSRIs, as its primary pharmacological action is thought to be norepinephrine-dopamine reuptake inhibition...

(Wellbutrin, Zyban) are typically much less reinforcing than faster acting ones which produce a rush like cocaine. In fact, bupropion is often used as a maintenance therapy

Maintenance therapy

Maintenance therapy is a medical therapy that is designed to help a primary treatment succeed. For example, maintenance chemotherapy may be given to people who have a cancer in remission in an attempt to prevent a relapse...

for treating stimulant

Stimulant

addiction

Substance dependence

The section about substance dependence in the Diagnostic and Statistical Manual of Mental Disorders does not use the word addiction at all. It explains:...

. However, depending on the route of administration

Route of administration

A route of administration in pharmacology and toxicology is the path by which a drug, fluid, poison, or other substance is taken into the body.-Classification:Routes of administration are usually classified by application location...

(e.g., insufflation

Insufflation

In religious and magical practice, insufflation and exsufflation are ritual acts of blowing, breathing, hissing, or puffing that signify variously expulsion or renunciation of evil or of the devil , or infilling or blessing with good .In historical Christian practice, such blowing appears most...

, inhalation

Inhalation

Inhalation is the movement of air from the external environment, through the air ways, and into the alveoli....

, or injection

Injection (medicine)

An injection is an infusion method of putting fluid into the body, usually with a hollow needle and a syringe which is pierced through the skin to a sufficient depth for the material to be forced into the body...

), the pleasurable

Pleasure

Pleasure describes the broad class of mental states that humans and other animals experience as positive, enjoyable, or worth seeking. It includes more specific mental states such as happiness, entertainment, enjoyment, ecstasy, and euphoria...

effects of the DRI in question can be dramatically enhanced, potentially rendering those with only mild rewarding effects to become far more reinforcing than they would be under normal circumstances.

List of DRIs

Of the above listed agents, altropane, amfonelic acid, benocyclidine, DBL-583, difluoropine, GBR-12,935, ioflupane, and vanoxerine are all highly selective, pure DRIs, with no known significant affinity for the serotonin or norepinephrine transporters or any other sites.

Dopamine releasing agents (DRAs) such as amphetamine

Amphetamine

and methamphetamine

Methamphetamine

Methamphetamine is a psychostimulant of the phenethylamine and amphetamine class of psychoactive drugs...

also function as DRIs secondary to their releasing action. To distinguish between DRIs and DRAs, the latter are not included in the above list. For a list of DRAs, see the releasing agent

Releasing agent

article. In correspondence with the previous paragraph, notably, to date, there are no known selective DRAs, as dissociating affinity between the dopamine and norepinephrine transporters has so far proven to be virtually impossible to achieve, likely on account of the very similar structure of the respective proteins.

Indications

General

Overdose

Abuse

List of DRIs

See also