PharmGKB: The Pharmacogenomics Knowledge Base

Drug/Small Molecule:
bupropion

2D structure

Overview

Generic Names: Amfebutamone; Bupropion Hcl
Trade Names: Wellbatrin; Wellbutrin; Wellbutrin SR; Wellbutrin XL; Zyban
PharmGKB Accession Id: PA448687

Description

A unicyclic, aminoketone antidepressant. The mechanism of its therapeutic actions is not well understood, but it does appear to block dopamine uptake. The hydrochloride is available as an aid to smoking cessation treatment. PubChem (source: Drug Bank)

Indication

For the treatment of depression and as aid to smoking cessation. (source: Drug Bank)

ATC Therapeutic Category

  • N07BA:Drugs used in nicotine dependence

Pharmacology, Interactions, and Contraindications

Mechanism Of Action

Bupropion selectively inhibits the neuronal reuptake of dopamine, norepinephrine, and serotonin; actions on dopaminergic systems are more significant than imipramine or amitriptyline whereas the blockade of norepinephrine and serotonin reuptake at the neuronal membrane is weaker for bupropion than for tricyclic antidepressants. The increase in norepinephrine may attenuate nicotine withdrawal symptoms and the increase in dopamine at neuronal sites may reduce nicotine cravings and the urge to smoke. Bupropion exhibits moderate anticholinergic effects. (source: Drug Bank)

Pharmacology

Bupropion, an antidepressant of the aminoketone class and a non-nicotine aid to smoking cessation, is chemically unrelated to tricyclic, tetracyclic, selective serotonin re-uptake inhibitor, or other known antidepressant agents. Compared to classical tricyclic antidepressants, Bupropion is a relatively weak inhibitor of the neuronal uptake of norepinephrine, serotonin, and dopamine. In addition, Bupropion does not inhibit monoamine oxidase. Bupropion produces dose-related central nervous system (CNS) stimulant effects in animals, as evidenced by increased locomotor activity, increased rates of responding in various schedule-controlled operant behavior tasks, and, at high doses, induction of mild stereotyped behavior. (source: Drug Bank)

Food Interactions

Avoid St.John's Wort.
Avoid alcohol.
Take without regard to meals. (source: Drug Bank)

Absorption, Distribution, Metabolism, Elimination & Toxicity

Biotransformation

Reduction of the carbonyl groupand/or hydroxylation of the tert-butyl group of bupropion. (source: Drug Bank)

Protein Binding

84 % (source: Drug Bank)

Absorption

For sustained release, peak plasma concentrations are achieved within 3 hours. (source: Drug Bank)

Toxicity

Symptoms of overdose include seizures, hallucinations, loss of consciousness, tachycardia, and cardiac arrest. (source: Drug Bank)

Isomeric SMILES Code:

CC(C(=O)c1cccc(c1)Cl)NC(C)(C)C (source: Drug Bank)

In-Depth Annotations (In-Depth Annotation)

  1. rs1800497 at chr11:112776038 in ANKK1
    Associated with 12-month smoking cessation outcomes following treatment with a combination of bupropion and behavioral counseling in women.
    Variant Name:
    DRD2:Taq1A; DRD2:32806C>T
    Related Drugs:
    bupropion
    Evidence:
    http://www.pharmgkb.org/.../variant.jsp
  2. rs2279343 at chr19:46207103 in CYP2A7P1, CYP2B6
    This variant is found alone as the CYP2B6*4 allele and also in combination as part of several other haplotypes. It has higher expression levels than other variants but its phenotype with respect to drugs is unclear. See VIP annotation for more details.
    Variant Name:
    CYP2B6:785A>G; CYP2B6:Lys262Arg; CYP2B6*4
    Related Drugs:
    bupropion
    Evidence:
    http://www.pharmgkb.org/.../variant.jsp
  3. rs28399499 at chr19:46210061 in CYP2A7P1, CYP2B6
    This variant is the only protein coding change in the CYP2B6*18 allele. Its phenotype with respect to drugs is unclear. See VIP annotation for more details.
    Variant Name:
    CYP2B6:983T>C; CYP2B6:Ile328Thr; part of CYP2B6*18
    Related Drugs:
    bupropion, efavirenz, nevirapine
    Evidence:
    http://www.pharmgkb.org/.../variant.jsp
  4. rs3211371 at chr19:46214555 in CYP2A7P1, CYP2B6
    CYP2B6:1459C>T has been reported to reduce CYP2B6 protein expression in human liver and brain. Impact on drug response is somewhat contradictory, see VIP annotation for details.
    Variant Name:
    CYP2B6:1459C>T; CYP2B6:Arg487Cys; part of CYP2B6*1C, CYP2B6*5, CYP2B6*7
    Related Drugs:
    bupropion, efavirenz, mephenytoin, nevirapine, nicotine
    Evidence:
    http://www.pharmgkb.org/.../variant.jsp

Curated Annotations (Curated Annotation)

  1. rs1800497 at chr11:112776038 in ANKK1
    This variant (A2/A2 genotype) is associated with improved response to bupropion efficacy for smoking cessation.
    Variant Name:
    DRD2 Taq1A
    Related Drugs:
    bupropion
    Related Diseases:
    Tobacco Use Disorder
    Evidence:
    PMID:18058343
  2. rs1800497 at chr11:112776038 in ANKK1
    Risk or phenotype-associated genotype: T. Phenotype: Compared to women who carry both A2 (CC) alleles, women with at least one A1 (T) allele were more likely to report having stopped taking bupropion due to medication side effects (odds ratio (OR)=1.91, 95% confidence interval (CI)=1.01-3.60; P<0.04) and at 12 months were somewhat more likely to report smoking (OR=0.76, 95% CI=0.56-1.03; P<0.076). Significant associations or trends were not observed in men. Study size: 451 participants. Study population: Caucasian.
    Variant Name:
    Taq1A (32806C>T)
    Related Drugs:
    bupropion
    Related Diseases:
    Tobacco Use Disorder
    Evidence:
    PMID:15492764
  3. rs1799732 at chr11:112851462 in DRD2
    A double-blind placebo-controlled trial of bupropion (n=414) found a statistically significant interaction of the - 141C Ins/Del genotype with the bupropion treatment group (OR=4.99; 95% CI=1.42, 17.62; p=0.01). Bupropion was more effective for patients who were homozygous for the Ins allele. In an open label trial of transdermal nicotine vs nicotine nasal spray (n=368), the participants with Ins/Ins genotypes were about one-half as likely to be abstinent at the end of treatment as participants with Ins/Del or Del/Del genotypes (OR=0.44; CI=0.25, 0.79; p=0.006).
    Variant Name:
    DRD2: -141C Ins/Del
    Related Drugs:
    bupropion
    Related Diseases:
    Tobacco Use Disorder
    Evidence:
    PMID:16123753
  4. rs34223104 at chr19:46188969 in CYP2A7P1, CYP2B6
    Risk or phenotype-associated allele: C. Phenotype: CYP2B6 mRNA expression and bupropion hydroxylase activity were approximately 2-fold higher in livers genotyped -82TC as in those genotyped -82TT. Study size: 85 (expression); 77 (activity). Study population/ethnicity: Non-tumorous liver samples from White individuals, Germany. Significance metric(s): p = 0.007 (expression); p = 0.042 (activity). Type of association: FA; PD
    Variant Name:
    CYP2B6:(-82)C>T, defining SNP of CYP2B6*22
    Related Drugs:
    bupropion
    Evidence:
    PMID:15722458
  5. rs12721655 at chr19:46202122 in CYP2A7P1, CYP2B6
    This variant was found as a single mutant, defining the *8 allele, and more often as triple mutant (*13; K139E + Q172H+ K262R ) on a *6 background. This variant had no detectable expression or activity in a COS-1 cell expression system.
    Variant Name:
    CYP2B6: 415A>G; K139E
    Related Drugs:
    bupropion
    Evidence:
    PMID:14551287
    PMID:15190123
    PMID:17638512
  6. rs2279343 at chr19:46207103 in CYP2A7P1, CYP2B6
    The CYP2B6*4 allele has been associated with increased activity against both nicotine and bupropion substrates.
    Variant Name:
    CYP2B6:K262R, CYP2B6:18053A>G, CYP2B6*4, part of CYP2B6*6
    Related Drugs:
    bupropion, nicotine
    Evidence:
    PMID:14515060
    PMID:17015050
    PMID:18695978
  7. rs737865 at chr22:18310121 in COMT, TXNRD2
    This variant may predict a favorable outcome for bupropion treatment for smoking cessation
    Related Drugs:
    bupropion
    Related Diseases:
    Tobacco Use Disorder
    Evidence:
    PMID:16876132
  8. rs165599 at chr22:18336781 in ARVCF, COMT
    This variant may predict a favorable outcome for bupropion treatment for smoking cessation
    Related Drugs:
    bupropion
    Related Diseases:
    Tobacco Use Disorder
    Evidence:
    PMID:16876132
Variant names are different names that have been used in the literature and other resources to refer to the same variant.

The following genes are in curated knowledge about this drug.

  Gene Relationship Evidence
No phenotype data No genotype data Literature annotations available Not annotated
ANKK1
  • CO
  •   
  •   
  •   
  • GN
Publications, Variants
No phenotype data Genotype Data Available No literature annotations Not annotated
ARVCF
  •   
  •   
  •   
  •   
  •   
Variants
No phenotype data Genotype Data Available Literature annotations available Not annotated
CHAT
  •   
  •   
  •   
  •   
  • GN
Publications
No phenotype data No genotype data Literature annotations available Not annotated
CHRNA2
  •   
  •   
  •   
  •   
  • GN
Publications
No phenotype data No genotype data Literature annotations available Not annotated
CHRNA5
  •   
  •   
  •   
  •   
  • GN
Publications
No phenotype data No genotype data Literature annotations available Not annotated
CHRNB2
  • CO
  •   
  •   
  •   
  • GN
Publications
Phenotype data available Genotype Data Available Literature annotations available Has annotations
COMT
  •   
  •   
  •   
  •   
  •   
Variants
No phenotype data Genotype Data Available Literature annotations available Has annotations
CYP2A6
  •   
  •   
  • PK
  •   
  • GN
Publications
No phenotype data Genotype Data Available No literature annotations Not annotated
CYP2A7P1
  •   
  •   
  •   
  •   
  •   
Variants
Phenotype data available Genotype Data Available Literature annotations available Has annotations
CYP2B6
  • CO
  • PD
  • PK
  • FA
  • GN
Publications, Variants
Phenotype data available Genotype Data Available Literature annotations available Has annotations
CYP2D6
  •   
  • PD
  • PK
  •   
  •   
Publications
Phenotype data available Genotype Data Available Literature annotations available Has annotations
CYP3A4
  • CO
  • PD
  • PK
  • FA
  • GN
Publications
No phenotype data No genotype data Literature annotations available Not annotated
DBH
  • CO
  •   
  •   
  •   
  • GN
Publications
No phenotype data No genotype data Literature annotations available Has annotations
DRD2
  • CO
  • PD
  • PK
  •   
  • GN
Publications, Variants
No phenotype data No genotype data Literature annotations available Not annotated
DRD4
  •   
  •   
  •   
  •   
  • GN
Publications
Phenotype data available Genotype Data Available Literature annotations available Has annotations
NR1I2
  • CO
  • PD
  • PK
  • FA
  • GN
Publications
No phenotype data Genotype Data Available Literature annotations available Not annotated
NR1I3
  • CO
  • PD
  • PK
  •   
  • GN
Publications
No phenotype data Genotype Data Available No literature annotations Not annotated
TXNRD2
  •   
  •   
  •   
  •   
  •   
Variants
Phenotype data available Genotype Data Available Literature annotations available Has annotations
UGT1A1
  • CO
  • PD
  • PK
  •   
  • GN
Publications

A list of non-curated publications that mention this drug along with other genes is available.

Drug Targets

Gene Description
SLC6A3 Uncurated Annotation (source: Drug Bank)
SLC6A2 Uncurated Annotation (source: Drug Bank)

The following drugs are in curated knowledge about this drug.

  Drug Relationship Evidence
Phenotype data available No genotype data Literature annotations available Not annotated
desipramine
  •   
  •   
  • PK
  •   
  •   
Publications
Phenotype data available No genotype data Literature annotations available Not annotated
fluoxetine
  •   
  •   
  •   
  • FA
  •   
Publications
No phenotype data No genotype data Literature annotations available Not annotated
fluvoxamine
  •   
  •   
  •   
  • FA
  •   
Publications
No phenotype data No genotype data Literature annotations available Not annotated
nefazodone
  •   
  •   
  •   
  • FA
  •   
Publications
No phenotype data No genotype data Literature annotations available Not annotated
paroxetine
  •   
  •   
  •   
  • FA
  •   
Publications
No phenotype data No genotype data Literature annotations available Not annotated
sertraline
  •   
  •   
  •   
  • FA
  •   
Publications
Phenotype data available Genotype Data Available Literature annotations available Not annotated
tamoxifen
  •   
  •   
  • PK
  •   
  •   
Publications

A list of non-curated publications that mention this drug along with other drugs is available.

Drug Interactions

Drug Description
carbamazepine Uncurated Annotation Carbamazepine decreases the effect of bupropion (source: Drug Bank)
cyclosporine Uncurated Annotation Decreases the effect of cyclosporine (source: Drug Bank)
isocarboxazid Uncurated Annotation Possible severe adverse reaction with this combination (source: Drug Bank)
phenelzine Uncurated Annotation Possible severe adverse reaction with this combination (source: Drug Bank)
rifabutin Uncurated Annotation Rifampin reduces bupropion levels (source: Drug Bank)
rifampin Uncurated Annotation Rifampin reduces bupropion levels (source: Drug Bank)
ritonavir Uncurated Annotation Ritonavir increases the effect and toxicity of bupropion (source: Drug Bank)
thioridazine Uncurated Annotation Inceases the effect and toxicity of thioridazine (source: Drug Bank)
tranylcypromine Uncurated Annotation Possible severe adverse reaction with this combination (source: Drug Bank)

Curated Information

The following diseases are in curated knowledge about this drug.

  Disease Relationship Evidence
Phenotype data available No genotype data Literature annotations available Not annotated
Depression
  •   
  • PD
  • PK
  •   
  • GN
Publications
No phenotype data No genotype data Literature annotations available Not annotated
HIV
  • CO
  • PD
  • PK
  •   
  • GN
Publications
Phenotype data available Genotype Data Available Literature annotations available Not annotated
Leukemia
  • CO
  • PD
  • PK
  •   
  • GN
Publications
No phenotype data No genotype data Literature annotations available Not annotated
Tobacco Use Disorder
  • CO
  •   
  • PK
  •   
  • GN
Publications, Variants

Non-Curated Information

A list of non-curated publications that mention this drug along with other diseases is available.

LinkOuts

Web Resource:
Wikipedia
DrugBank:
DB01156
ChEBI ID:
3219
KEGG Compound ID:
C06860
KEGG Drug ID:
D07591
PubChem Compound ID:
444
PubChem Substance ID:
178415

Common Searches

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Non-Curated Publications

A list of non-curated publications that mention this drug is available.

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