Bupropion

Bupropion
ATC Code N06AX12, N07BA02
Formula C13H18ClNO
Molar Mass (g·mol−1) 239,74
Physical State solid
Melting Point (°C) 233–234
PKS Value 8.35
CAS Number 34911-55-2
PUB Number 444
Drugbank ID DB01156
Solubility soluble in water

Basics

Bupropion is an antidepressant used primarily for the treatment of major depressive disorder and to aid in smoking cessation. It is also used as an add-on treatment for "incomplete response" to first-line antidepressant.

Bupropion was invented in 1969 by Nariman Mehta, who worked at the Burroughs Wellcome company. It was first approved for medical use in the United States in 1985. It is on the World Health Organization's list of essential medicines.

Pharmacology

Pharmacodynamics and mechanism of action

Bupropion is a norepinephrine and dopamine reuptake inhibitor that exerts its pharmacological effects by binding and inhibiting the enzymes involved in the uptake of the neurotransmitters norepinephrine and dopamine from the synaptic cleft, thereby prolonging their duration of action within the neuronal synapse and the downstream effects of these neurotransmitters.

When used as a smoking cessation agent, bupropion, by inhibiting dopamine reuptake, affects the reward system in the brain. In addition, it appears to have a mild antagonistic effect at the nicotinic acetylcholinergic receptor (AChR). This attenuates the overall effect of nicotine and decreases the craving to smoke.

From a chemical point of view, bupropion is not related to tricyclic, tetracyclic, selective serotonin reuptake inhibitors or other known antidepressants. Therefore, it is classified from the group of "atypical antidepressants". It has no clinically relevant serotonergic effects and no effects on histamine or epinephrine receptors. The lack of activity at these receptors results in a more tolerable side effect profile; for example, compared with SSRIs or TCAs, bupropion causes fewer sexual side effects, sedation, or weight gain.

Pharmacokinetics

Following oral administration, bupropion is rapidly and completely absorbed, reaching maximum blood plasma concentration after 1.5 hours. Sustained release formulations, delay the time to maximum drug concentration to 3 -5 hours. The absolute bioavailability of bupropion is not precisely known, but is estimated to be relatively low at 5-20% due to the very strong first-pass effect.

Bupropion is metabolized in the body via several pathways. The oxidative pathway leads via the cytochrome P450 isozymes CYP2B6 and CYP2C19. The reductive pathway leads to the respective breakdown products via the enzyme 11β-hydroxysteroid dehydrogenase type 1 in the liver and the enzyme AKR7A2/AKR7A3 in the intestine. Some of the metabolites of bupropion are also pharmacologically active and contribute to the effects of the substance. Bupropion is almost completely metabolized and excreted in the urine and stool.

Drug interactions

Drug interactions are possible with CYP2B6 inhibitors: these include drugs such as paroxetine, sertraline, norfluoxetine, diazepam, clopidogrel, and orphenadrine. Concomitant use results in an increase in bupropion blood concentration. Concomitant use with CYP2B6 inducers such as carbamazepine, clotrimazole, rifampicin, ritonavir, St. John's wort, and phenobarbital is expected to result in lower bupropion levels and reduced efficacy. Bupropion and its metabolites are inhibitors of CYP2D6. This may result in interactions with substances that are degraded by this enzyme.

Toxicity

Adverse drug reactions

Bupropion has several properties that distinguish it from other antidepressants: It does not usually cause sexual dysfunction, and it is not associated with weight gain and drowsiness. However, bupropion carries a much higher risk of seizures than many other antidepressants, so extreme caution is advised in patients with a history of seizures.

More common bupropion side effects include:

  • Dry mouth
  • Sore throat
  • Stuffy nose
  • Ringing in the ears
  • Blurred vision
  • Nausea
  • Vomiting
  • Stomach pain
  • Loss of appetite
  • Constipation
  • Sleep problems
  • Shaking
  • Sweating
  • Anxiety and nervousness
  • Fast heartbeat
  • Confusion
  • Restlessness
  • Aggressiveness
  • Rash
  • Weight loss
  • Increased urination
  • Headache and dizziness
  • Muscle or joint pain

Contraindications and precautions

Bupropion should not be taken if allergy is known or if the following conditions exist:

  • Epilepsy
  • An eating disorder such as anorexia or bulimia nervosa
  • After discontinuation of therapy with sedatives such as Xanax or antiepileptic drugs
  • In cold turkey alcohol withdrawal
  • MAO inhibitor therapy

After therapy with MAO inhibitors, there must be an interval of at least 14 days before taking bupropion. A dangerous interaction could occur. MAO inhibitors include the drugs: Isocarboxazid, Linezolid, Phenelzine, Rasagiline, Selegiline, and Tranylcypromine.

Markus Falkenstätter

Markus Falkenstätter
Author

Markus Falkenstätter ist Autor zu pharmazeutischen Themen in der Medizin-Redaktion von Medikamio. Er befindet sich im letzten Semester seines Pharmaziestudiums an der Universität Wien und liebt das wissenschaftliche Arbeiten im Bereich der Naturwissenschaften.

Mag. pharm Stefanie Lehenauer

Mag. pharm Stefanie Lehenauer
Lector

Stefanie Lehenauer ist seit 2020 freie Autorin bei Medikamio und studierte Pharmazie an der Universität Wien. Sie arbeitet als Apothekerin in Wien und ihre Leidenschaft sind pflanzliche Arzneimittel und deren Wirkung.

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