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Dopamine Reuptake Inhibitors

Key Points

  • Dopamine reuptake inhibitors (DRIs) are a class of drugs that specifically inhibit the reuptake of dopamine, but not necessarily norepinephrine. Some DRIs also act on norepinephrine, but not all.
  • For some, DRIs can increase the levels of dopamine in the brain to improve concentration, attention, and executive function.
  • DRIs may have risks, including serious side effects, risk of overdose, potential for drug interactions, and withdrawal symptoms.
  • DRIs have a low potential for abuse, but cases of abuse have been reported.

Dopamine reuptake inhibitors (DRIs), also known as norepinephrine and dopamine reuptake inhibitors (NDRIs), are antidepressants that work with the norepinephrine and dopamine system in the brain, which is related to stress response, alertness, and feelings of motivation, reward, and pleasure. While there are benefits to DRIs for some people, there are some risks and side effects to be aware of.

Learn about dopamine reuptake inhibitors, their uses, and how to determine if they fit you.

What Are Dopamine Reuptake Inhibitors?

Dopamine reuptake inhibitors are a class of drugs that block the dopamine transporter, preventing dopamine from being reabsorbed. This mechanism leads to increased dopamine levels in the brain, which can improve concentration, attention, and executive function.[1]

DRIs are known as atypical antidepressants because they work differently from other types of antidepressants, specifically by inhibiting the reuptake of dopamine. Bupropion (Wellbutrin) is the most common DRI.[2]

How Do Dopamine Reuptake Inhibitors Work?

The mechanism of DRIs blocks the dopamine transporter, which prevents dopamine from reentering the brain cells that released it. This increases the dopamine concentration in the brain, leading to more active neurotransmitters and more dopamine availability for more neurons.[3] The result is more alertness, focus, and positive feelings, which can help with depression, anxiety, and other mental health conditions.

DRIs are similar to other reuptake inhibitor drugs, such as selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs). However, DRIs primarily focus on dopamine, and in some cases, norepinephrine.

Uses for DRIs

Uses for DRIsDRIs are often prescribed to treat depression and narcolepsy. They may be prescribed to help with cravings and effects in addiction recovery as well.

  • Depression: DRIs are commonly used to treat depression, particularly in cases where low dopamine activity is implicated.[4] DRIs can help by increasing the availability of dopamine in the brain. Unlike selective serotonin reuptake inhibitors (SSRIs), DRIs typically have a lower incidence of sexual dysfunction or weight gain.
  • Smoking cessation: DRIs may be used to help people quit smoking.[5] It can decrease withdrawal symptoms and simulate the effects of nicotine on dopamine and noradrenaline systems. It also blocks nicotine receptors. Typically, DRIs are used alongside therapies for the best outcomes.
  • Cocaine addiction: Cocaine and other stimulants inhibit dopamine reuptake, causing euphoria. DRIs may be used to treat cocaine addiction and decrease the physical dependence on the drug and the feelings of euphoria that encourage use.[6]

DRIs may be used off-label, which is when drugs are prescribed for a different purpose than what the FDA approved. Common off-label uses for DRIs are for attention deficit hyperactivity disorder (ADHD) and neuropathic pain.

Side Effects of DRIs

DRIs are generally safe when used as prescribed, but they do have some common side effects:[7]

  • Anxiety
  • Dry mouth
  • Hyperventilation
  • Irregular heartbeats
  • Irritability
  • Restlessness
  • Shaking
  • Trouble sleeping

Though less common, DRIs can cause severe headaches, skin rashes or itching, and a buzzing or ringing in the ears. Rare side effects include confusion, fainting, paranoia, seizures, trouble concentrating, delusions, and seeing, hearing, or feeling things that aren’t there.

DRI Risks and Interactions

Dopamine reuptake inhibitors have some risks to be aware of, including a risk of seizures and insomnia.

DRIs may interact with other drugs, including monoamine oxidase inhibitors, tricyclic antidepressants, levodopa, amantadine, antipsychotics, beta-blockers, antiarrhythmics, theophylline, and certain SSRIs.[8] Combining DRIs with these drugs can cause worsening side effects, seizures, toxicity, or hypertensive crisis, a potentially life-threatening condition.

There’s a potential for overdose (toxicity) with DRIs, especially if they’re combined with certain drugs. Some of the symptoms of toxicity include:[9]

  • Seizures
  • Loss of consciousness
  • Tachycardia
  • Irregular heart rate (arrhythmia)
  • Cardiac failure
  • Hallucinations

If you suspect someone is overdosing, call 911 immediately and wait for help to arrive. There’s no specific antidote for DRI overdose, but the person may be able to recover with prompt medical attention.

DRI Withdrawal

Prolonged use of DRIs can cause physical dependence, which is when the body requires the drug to function normally. Stopping DRI use or reducing the dose can cause withdrawal symptoms like:[10]

  • Irritability
  • Anxiety
  • Headaches
  • Dizziness
  • Insomnia
  • Tiredness
  • Nausea
  • Vomiting
  • Appetite changes
  • Flu-like symptoms
  • Sensations like electric shocks

The onset and duration of withdrawal depend on how long you’ve been on the medication, your dose, and other factors, but most people have a mild withdrawal that sets in a few days after the last dose and lasts one to two weeks.

If you want to stop taking DRIs or reduce your dose, speak to your doctor. They can recommend a taper schedule to “wean” you off the drug over several weeks to reduce the likelihood of withdrawal symptoms.

Dopamine Reuptake Inhibitors Abuse Potential

DRIs have a low potential for abuse, but there are cases of misuse to get high. Athletes have abused DRIs to achieve euphoria, and inmates in correctional facilities have relied on bupropion instead of benzodiazepines and stimulants because of its availability.[11]

People who abuse DRIs may take more pills or higher doses at once, though some have crushed the pills and snorted the powder. These people claim that DRIs have a similar effect to cocaine.

There are risks to abusing DRIs, such as psychotic symptoms, seizures, cardiotoxicity, and severe withdrawal symptoms.

Like other substances, DRI abuse is best addressed with medical detoxification or detox. This environment offers comfort and safety with 24-hour medical supervision and care to minimize the risks of withdrawal or complications while minimizing pain, discomfort, and the chance of relapse.

Seeking Help for DRI Abuse

Most people who take DRIs do so with a prescription from their doctors to manage depression or other conditions. However, there is a risk of dependence and abuse with DRIs, which should be addressed with detox and addiction treatment to avoid withdrawal and complications.

Frequently Asked Questions

Below are some of the most frequently asked questions regarding DRIs

Norepinephrine dopamine reuptake inhibitors (NDRIs) are a type of antidepressant medication that can alleviate the symptoms of depression, anxiety, and other conditions.

Wellbutrin (bupropion) can boost the levels of dopamine and norepinephrine. It can be effective for treating mental health conditions like depression, but it’s also used as part of comprehensive addiction treatment for nicotine and cocaine to reduce cravings.

No. Unlike stimulant drugs that work almost immediately, Wellbutrin takes time to build up in the system and take effect. However, the increase in dopamine that Wellbutrin can stimulate may give people a natural energy boost.

There’s a potential for physical dependence and withdrawal with regular use of NDRIs. If you take it for a long period or at a high dose, then suddenly stop or reduce the dose, it can bring on withdrawal symptoms like headache, irritability, and more.

SSRIs are often preferred over NDRIs because they have fewer side effects and affect different brain chemicals, but not every drug works for everyone. If SSRIs aren’t effective or cause side effects, NDRIs may be tried.

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[1] Norepinephrine-dopamine reuptake inhibitor. Norepinephrine-Dopamine Reuptake Inhibitor – an overview | ScienceDirect Topics. (n.d.). Retrieved from https://www.sciencedirect.com/topics/medicine-and-dentistry/norepinephrine-dopamine-reuptake-inhibitor#:~:text=A%20dopamine%20reuptake%20inhibitor%20acts,regions%20(i.e.%2C%20DLPFC) on 2024, May 9.

[2] Dopamine reuptake inhibitor. Dopamine Reuptake Inhibitor – an overview | ScienceDirect Topics. (n.d.). Retrieved from https://www.sciencedirect.com/topics/pharmacology-toxicology-and-pharmaceutical-science/dopamine-reuptake-inhibitor on 2024, May 9.

[3] Dopamine reuptake inhibitor. Dopamine Reuptake Inhibitor – an overview | ScienceDirect Topics. (n.d.). Retrieved from https://www.sciencedirect.com/topics/pharmacology-toxicology-and-pharmaceutical-science/dopamine-reuptake-inhibitor on 2024, May 9.

[4,5] Bupropion: Uses, dosage, side effects. Drugs.com. (n.d.). Retrieved from https://www.drugs.com/bupropion.html on 2024, May 9.

[6] Galloway, M. P., Westerink, B. H., Rothman, R. B., Ritz, M. C., Wise, R. A., Madras, B. K., Spealman, R. D., & Bergman, J. (2002, November 4). High affinity dopamine reuptake inhibitors as potential cocaine antagonists: A strategy for drug development. Life Sciences. Retrieved from https://www.sciencedirect.com/science/article/abs/pii/0024320590904665 on 2024, May 9.

[7] Mayo Foundation for Medical Education and Research. (2024, May 1). Bupropion (oral route) side effects. Mayo Clinic. Retrieved from https://www.mayoclinic.org/drugs-supplements/bupropion-oral-route/side-effects/drg-20062478 on 2024, May 9.

[8] Google. (n.d.). Clinical psychopharmacology. Google Books. Retrieved from https://books.google.com/books?id=i9p1DwAAQBAJ&pg=PA23&dq=Norepinephrine%2Band%2BDopamine%2BReuptake%2BInhibitors&hl=en&sa=X&ved=0ahUKEwjw4OfooZvgAhWqiVQKHRb4BMM4ChDoAQguMAE#v=onepage&q=Norepinephrine%20and%20Dopamine%20Reuptake%20Inhibitors&f=false on 2024, May 9.

[9] Alberter, A. A. (2022, December 12). Bupropion toxicity. StatPearls [Internet]. Retrieved from https://www.ncbi.nlm.nih.gov/books/NBK580478/#:~:text=Bupropion%20is%20a%20medication%20primarily,resulting%20in%20dysthymias%20and%20seizures on 2024, May 9.

[10] Warner, C. H., Bobo, W., Warner, C., Reid, S., & Rachal, J. (2006, August 1). Antidepressant discontinuation syndrome. American Family Physician. Retrieved from https://www.aafp.org/pubs/afp/issues/2006/0801/p449.html on 2024, May 9.

[11] Evans, E. A., & Sullivan, M. A. (2014, August 14). Abuse and misuse of antidepressants. Substance abuse and rehabilitation. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4140701/ on 2024, May 9.

Last medically reviewed May 27, 2024.