Bupropion hydrochlorideProduct ingredient for Bupropion

Name
Bupropion hydrochloride
Drug Entry
Bupropion

Bupropion (also known as the brand name product Wellbutrin®) is a norepinephrine/dopamine-reuptake inhibitor (NDRI) used most commonly for the management of Major Depressive Disorder (MDD), Seasonal Affective Disorder (SAD), and as an aid for smoking cessation. Bupropion exerts its pharmacological effects by weakly inhibiting the enzymes involved in the uptake of the neurotransmitters norepinephrine and dopamine from the synaptic cleft, therefore prolonging their duration of action within the neuronal synapse and the downstream effects of these neurotransmitters. More specifically, bupropion binds to the norepinephrine transporter (NET) and the dopamine transporter (DAT).8,12

Bupropion was originally classified as an "atypical" antidepressant because it does not exert the same effects as the classical antidepressants such as Monoamine Oxidase Inhibitors (MAOIs), Tricyclic Antidepressants (TCAs), or Selective Serotonin Reuptake Inhibitors (SSRIs). While it has comparable effectiveness to typical first-line options for the treatment of depression such as SSRIs,9,10 bupropion is a unique option for the treatment of MDD as it lacks any clinically relevant serotonergic effects, typical of other mood medications, or any effects on histamine or adrenaline receptors.8 Lack of activity at these receptors results in a more tolerable side effect profile; bupropion is less likely to cause sexual side effects, sedation, or weight gain as compared to SSRIs or TCAs, for example.10,11

When used as an aid to smoking cessation, bupropion is thought to confer its anti-craving and anti-withdrawal effects by inhibiting dopamine reuptake, which is thought to be involved in the reward pathways associated with nicotine, and through the antagonism of the nicotinic acetylcholinergic receptor.15,1,14 A Cochrane Review of meta-analyses of available treatment modalities for smoking cessation found that abstinence rates approximately doubled when bupropion was used as compared to placebo, and was found to have similar rates of smoking cessation as nicotine replacement therapy (NRT).13

Bupropion is sometimes used as an add-on agent to first-line treatments of depression such as selective serotonin reuptake inhibitor (SSRI) medications when there is a treatment-failure or only partial response.7 Bupropion is also used off-label for the management of Attention/Deficit-Hyperactivity Disorder (ADHD) in adults with comorbid bipolar depression to avoid mood destabilization caused by typical stimulant medications used for the treatment of ADHD.25

When used in combination with naltrexone in the marketed product ContraveⓇ for chronic weight management, the two components are thought to have effects on areas of the brain involved in the regulation of food intake. This includes the hypothalamus, which is involved in appetite regulation, and the mesolimbic dopamine circuit, which is involved in reward pathways.24 Studies have shown that the combined activity of bupropion and naltrexone increase the firing rate of hypothalamic pro-opiomelanocortin (POMC) neurons and blockade of opioid receptor-mediated POMC auto-inhibition, which are associated with a reduction in food intake and increased energy expenditure.24,20,22 The combination of naltrexone and bupropion was shown to result in a statistically significant weight loss, with a mean change in body weight of -6.3% compared to -1.3% for placebo.21

Accession Number
DBSALT000199
Structure
Thumb
Synonyms
Bupropion HCl
UNII
ZG7E5POY8O
CAS Number
31677-93-7
Weight
Average: 276.202
Monoisotopic: 275.084369649
Chemical Formula
C13H19Cl2NO
InChI Key
HEYVINCGKDONRU-UHFFFAOYSA-N
InChI
InChI=1S/C13H18ClNO.ClH/c1-9(15-13(2,3)4)12(16)10-6-5-7-11(14)8-10;/h5-9,15H,1-4H3;1H
IUPAC Name
2-(tert-butylamino)-1-(3-chlorophenyl)propan-1-one hydrochloride
SMILES
Cl.CC(NC(C)(C)C)C(=O)C1=CC(Cl)=CC=C1
External Links
PubChem Compound
62884
ChemSpider
56612
ChEBI
3220
ChEMBL
CHEMBL1698
Wikipedia
Bupropion
Predicted Properties
PropertyValueSource
Water Solubility0.0693 mg/mLALOGPS
logP3.28ALOGPS
logP3.27ChemAxon
logS-3.5ALOGPS
pKa (Strongest Acidic)18.29ChemAxon
pKa (Strongest Basic)8.22ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area29.1 Å2ChemAxon
Rotatable Bond Count4ChemAxon
Refractivity67.7 m3·mol-1ChemAxon
Polarizability26.21 Å3ChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon