Bupropion

2-(tert-butylamino)-1-(3-chlorophenyl)propan-1-one

Overview

Bupropion belongs to Stimulants.

Key safety note: Bupropion's signature risk is a dose-dependent lowering of the seizure threshold: seizure incidence is low (~0.1%) at ≤300 mg/day of the slow-release forms but climbs sharply at higher doses and with the old immediate-release product.[3][2][4]
Effects
Subjective effects vary. What a substance feels like depends on dose, individual physiology, mindset, and setting. The points below describe commonly reported effects, not guaranteed, uniform, or desirable outcomes.
  • At therapeutic oral doses it is activating rather than euphoric, improved energy, motivation and concentration and relief of depressive symptoms, without the sedation, weight gain or sexual dysfunction typical of SSRIs.
  • Common stimulant-like side effects include insomnia, dry mouth, jitteriness or anxiety, headache and reduced appetite. These often ease over the first weeks of treatment.
  • It reduces nicotine craving and withdrawal symptoms, the basis of its smoking-cessation use.
  • In overdose or when misused by snorting or injection it can produce agitation, tachycardia, hallucinations and, characteristically, seizures.
Dosing & duration
Harm-reduction note: These are commonly cited reference ranges, not a recommendation or a “safe” dose. Potency, purity, body chemistry, tolerance, and drug combinations vary widely. Start low, go slow, wait for full effects before redosing, and never assume an unknown product matches these figures. Missing data is not evidence of safety.

Oral (immediate-release, sustained-release SR, extended-release XL). Prescription-only oral tablets in immediate-release (IR), sustained-release (SR) and extended-release (XL) forms. Slow-release dosing is preferred to cap peak concentrations and limit seizure risk. Single doses are kept low for the same reason. These are medical reference ranges, not recreational guidance.

Dose ranges

Depression (XL, once daily)

Start 150 mg/day → usual 300 mg/day (max 450 mg/day)

Smoking cessation (SR, as Zyban)

150 mg/day for 3 days, then 150 mg twice daily (max 300 mg/day), begin 1–2 weeks before quit date

Single-dose ceiling

≤150 mg (IR) or ≤200 mg (SR) per dose to limit peak levels

Duration

onset

Stimulant-like effects within hours, antidepressant response over ~1–4 weeks

total

Once- or twice-daily dosing (long-acting metabolites)

Chemical & Physical Properties
FormulaC13H18ClNO
Molar mass239.74 g/mol
StateSolid
Melting point233–234 °C (hydrochloride salt)
Boiling point52 °C at 0.005 mmHg (free base)
DensityNot reported
Vapor pressureNot reported
pKa8.35
LogP3.6
Solubility312 mg/ml, Very hygroscopic and susceptible to decomposition, Soluble in methanol, ethanol, acetone, ether, benzene
Refractive indexNot reported
Identifiers & Synonyms
CAS34911-55-2
CAS (enantiomer)
PubChem CID444
InChIKeySNPPWIUOZRMYNY-UHFFFAOYSA-N
InChIInChI=1S/C13H18ClNO/c1-9(15-13(2,3)4)12(16)10-6-5-7-11(14)8-10/h5-9,15H,1-4H3
SMILESCC(C(=O)C1=CC(=CC=C1)Cl)NC(C)(C)C

Synonyms

  • Wellbutrin
  • Zyban
  • Amfebutamone
Pharmacodynamics & Biochemistry

Bupropion is an aminoketone: structurally a substituted cathinone (essentially the 3-chloro, N-tert-butyl analogue of cathinone): used clinically as an atypical antidepressant and smoking-cessation aid rather than as a recreational stimulant. Its classical action is norepinephrine–dopamine reuptake inhibition (NDRI), blocking the norepinephrine (NET) and dopamine (DAT) transporters. Both actions are comparatively weak: at antidepressant doses (~300 mg/day) bupropion and its metabolites occupy only ~20% of striatal DAT, far below the >50% seen with methylphenidate, which is why it lacks the strong reinforcing 'rush' of cocaine or amphetamine despite sharing their molecular targets. Much of the activity is carried by metabolites rather than the parent drug. Hepatic CYP2B6 hydroxylates bupropion to hydroxybupropion, which circulates at roughly 20× the exposure (AUC) of the parent and is itself a reuptake inhibitor. Carbonyl reduction additionally yields threohydro- and erythrohydrobupropion. Because these metabolites so outweigh the parent, bupropion is sometimes described as a prodrug for hydroxybupropion. Independent of reuptake, bupropion (and hydroxybupropion) is a non-competitive antagonist / negative allosteric modulator of neuronal nicotinic acetylcholine receptors (nAChRs), most relevantly the α4β2 and α3β4 subtypes, at low-micromolar concentrations. This nAChR blockade is thought to underlie its efficacy for smoking cessation (marketed as Zyban) by blunting nicotine's rewarding effect and easing withdrawal. The nAChR IC50 values sit in the µM range and are described qualitatively here. Only the NET and DAT constants are quantified in the binding table. Bupropion is also a strong inhibitor of CYP2D6 (largely via hydroxybupropion), raising exposure to many co-administered CYP2D6 substrates (tricyclics, atomoxetine, metoprolol, some antipsychotics) and reducing activation of the prodrug tamoxifen. Its best-known liability is a dose-dependent lowering of the seizure threshold, which rises steeply above recommended doses and drove withdrawal of the original immediate-release product in favour of slow-release (SR/XL) formulations.

Biological targets

  • NET
  • DAT
  • nAChR

Binding & functional measurements

TargetMeasurementSpecies
NETpKi 6.4Human
Pharmacokinetics
BioavailabilityLow and variable due to extensive first-pass metabolism (~5–20%)
TmaxNot reported
Half-lifeParent ≈12–21 h, hydroxybupropion ≈20 h
VdNot reported
Protein binding≈84% (hydroxybupropion ≈77%)
MetabolismHepatic CYP2B6 → hydroxybupropion. Carbonyl reduction to threo-/erythrohydrobupropion
ExcretionMainly renal (~87% in urine, <1% unchanged). ~10% faecal
Toxicology & Safety
Harm-reduction note: Toxicity and risk depend on dose, route, purity, combinations, setting, and individual health factors. Missing harms should never be interpreted as evidence of safety.

Not reported

Bupropion's signature risk is a dose-dependent lowering of the seizure threshold: seizure incidence is low (~0.1%) at ≤300 mg/day of the slow-release forms but climbs sharply at higher doses and with the old immediate-release product. It is therefore contraindicated in seizure disorders and in bulimia or anorexia nervosa (where electrolyte disturbance further raises seizure risk) and during abrupt alcohol or benzodiazepine withdrawal, and must not be combined with MAOIs (hypertensive risk). Common effects are insomnia, dry mouth, agitation, headache, tremor and appetite loss. Unlike SSRIs it is broadly weight-neutral and tends to spare sexual function. As an antidepressant it carries the class warning for suicidal ideation in adolescents and young adults. Recreational misuse by insufflation or injection is reported ('poor man's cocaine') and is dangerous precisely because crushing or IV use delivers a seizure-threshold-lowering stimulant as a bolus. Ordinary oral therapeutic use has low abuse potential.[3][2][4]

Legal Status
Legal note: Legal status can change over time and may vary by country, region, formulation, analogue status, prescription context, and enforcement practice. Always confirm with current official sources before relying on this section.
Interactions & Contraindications

Drug interactions

MAOIs Contraindicated, risk of hypertensive reactions, separate by at least 14 days.[2]
CYP2D6 substrate drugs Bupropion strongly inhibits CYP2D6 and raises their levels (tricyclics, atomoxetine, metoprolol, some antipsychotics) and lowers activation of the prodrug tamoxifen.[3][2]
Drugs that lower the seizure threshold Additive seizure risk (antipsychotics, tramadol, theophylline, systemic stimulants, alcohol or benzodiazepine withdrawal).[2][4]
CYP2B6 / CYP3A4 inhibitors or inducers Inducers (ritonavir, efavirenz, carbamazepine) lower, and inhibitors (ticlopidine, clopidogrel) raise, bupropion and hydroxybupropion exposure.[2]

Contraindications

Current or prior seizure disorder current or prior seizure disorder.[2]
Current or past eating disorder (bulimia or anorexia) current or historical bulimia or anorexia nervosa.[2]
Combining with alcohol or other CNS depressants abrupt discontinuation of alcohol, benzodiazepines or other sedatives (seizure risk).[2]
Concurrent MAOI, SSRI/SNRI or other serotonergic medication concurrent or recent (within 14 days) MAOI use.[2]
Usage & Context
  • A first-line antidepressant for major depressive disorder and seasonal affective disorder, valued for being activating and for sparing weight and sexual function. Often added to an SSRI to counter SSRI-induced sexual dysfunction.
  • An FDA-approved smoking-cessation aid (Zyban), and, combined with naltrexone (Contrave), an adjunct for weight management.
  • Used off-label for adult ADHD and fatigue/apathy. Recreational misuse by snorting or injection is documented but uncommon and hazardous (seizures).
Sources & Evidence

Further Information