Bupropion
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Basic Info
| Common Name | Bupropion(F04785) |
| 2D Structure | |
| Description | Bupropion is a selective catecholamine (norepinephrine and dopamine) reuptake inhibitor. It has only a small effect on serotonin reuptake. It does not inhibit MAO. The antidepressant effect of bupropion is considered to be mediated by its dopaminergic and noradrenergic action. Bupropion has also been shown to act as a competitive alpha-3-beta-4- nicotinic antagonist, the alpha-3-beta-4-antagonism has been shown to interrupt addiction in studies of other drugs such as ibogaine. This alpha-3-beta-4-antagonism correlates quite well with the observed effect of interrupting addiction. 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; Bupropion is a selective catecholamine (norepinephrine and dopamine) reuptake inhibitor. It has only a small effect on serotonin reuptake. It does not inhibit MAO. The antidepressant effect of bupropion is considered to be mediated by its dopaminergic and noradrenergic action. Bupropion has also been shown to act as a competitive alpha-3-beta-4-nicotinic antagonist, the alpha-3-beta-4-antagonism has been shown to interrupt addiction in studies of other drugs such as ibogaine. This alpha-3-beta-4-antagonism correlates quite well with the observed effect of interrupting addiction. Bupropion (amfebutamone) (brand names Wellbutrin and Zyban) is an antidepressant of the aminoketone class, chemically unrelated to tricyclics or selective serotonin reuptake inhibitors (SSRIs). It is similar in structure to the stimulant cathinone, and to phenethylamines in general. It is a chemical derivative of diethylpropion, an amphetamine-like substance used as an anorectic. Bupropion is both a dopamine reuptake inhibitor and a norepinephrine reuptake inhibitor. It is often used as a smoking cessation aid. |
| FRCD ID | F04785 |
| CAS Number | 34911-55-2 |
| PubChem CID | 444 |
| Formula | C13H18ClNO |
| IUPAC Name | 2-(tert-butylamino)-1-(3-chlorophenyl)propan-1-one |
| InChI Key | SNPPWIUOZRMYNY-UHFFFAOYSA-N |
| InChI | InChI=1S/C13H18ClNO/c1-9(15-13(2,3)4)12(16)10-6-5-7-11(14)8-10/h5-9,15H,1-4H3 |
| Canonical SMILES | CC(C(=O)C1=CC(=CC=C1)Cl)NC(C)(C)C |
| Isomeric SMILES | CC(C(=O)C1=CC(=CC=C1)Cl)NC(C)(C)C |
| Wikipedia | Bupropion |
| Synonyms |
2-(tert-butylamino)-1-(3-chlorophenyl)propan-1-one
bupropion
Amfebutamone
34911-55-2
Amfebutamon
amfebutamonum
Amfebutamona
(+-)-Bupropion
Elontril
Wellbatrin
|
| Classifies |
Predicted: Illegal Additives
|
| Update Date | Nov 13, 2018 17:07 |
Chemical Taxonomy
| Kingdom | Organic compounds |
| Superclass | Organic oxygen compounds |
| Class | Organooxygen compounds |
| Subclass | Carbonyl compounds |
| Intermediate Tree Nodes | Ketones - Aryl ketones - Phenylketones |
| Direct Parent | Alkyl-phenylketones |
| Alternative Parents | |
| Molecular Framework | Aromatic homomonocyclic compounds |
| Substituents | Alkyl-phenylketone - Phenylpropane - Benzoyl - Aryl alkyl ketone - Chlorobenzene - Halobenzene - Aryl chloride - Aryl halide - Monocyclic benzene moiety - Benzenoid - Alpha-aminoketone - Secondary aliphatic amine - Secondary amine - Organochloride - Organohalogen compound - Organic oxide - Organopnictogen compound - Organic nitrogen compound - Amine - Organonitrogen compound - Hydrocarbon derivative - Aromatic homomonocyclic compound |
| Description | This compound belongs to the class of organic compounds known as alkyl-phenylketones. These are aromatic compounds containing a ketone substituted by one alkyl group, and a phenyl group. |
Properties
| Property Name | Property Value |
|---|---|
| Molecular Weight | 239.743 |
| Hydrogen Bond Donor Count | 1 |
| Hydrogen Bond Acceptor Count | 2 |
| Rotatable Bond Count | 4 |
| Complexity | 247 |
| Monoisotopic Mass | 239.108 |
| Exact Mass | 239.108 |
| XLogP | 3.2 |
| Formal Charge | 0 |
| Heavy Atom Count | 16 |
| Defined Atom Stereocenter Count | 0 |
| Undefined Atom Stereocenter Count | 1 |
| Defined Bond Stereocenter Count | 0 |
| Undefined Bond Stereocenter Count | 0 |
| Isotope Atom Count | 0 |
| Covalently-Bonded Unit Count | 1 |
ADMET
| Model | Result | Probability |
|---|---|---|
| Absorption | ||
| Blood-Brain Barrier | BBB+ | 0.9750 |
| Human Intestinal Absorption | HIA+ | 1.0000 |
| Caco-2 Permeability | Caco2+ | 0.8866 |
| P-glycoprotein Substrate | Non-substrate | 0.7330 |
| P-glycoprotein Inhibitor | Non-inhibitor | 0.8738 |
| Non-inhibitor | 0.9343 | |
| Renal Organic Cation Transporter | Non-inhibitor | 0.8814 |
| Distribution | ||
| Subcellular localization | Mitochondria | 0.5662 |
| Metabolism | ||
| CYP450 2C9 Substrate | Non-substrate | 0.7850 |
| CYP450 2D6 Substrate | Non-substrate | 0.9116 |
| CYP450 3A4 Substrate | Substrate | 0.5740 |
| CYP450 1A2 Inhibitor | Non-inhibitor | 0.7499 |
| CYP450 2C9 Inhibitor | Non-inhibitor | 0.9070 |
| CYP450 2D6 Inhibitor | Inhibitor | 0.8932 |
| CYP450 2C19 Inhibitor | Inhibitor | 0.8993 |
| CYP450 3A4 Inhibitor | Non-inhibitor | 0.7743 |
| CYP Inhibitory Promiscuity | High CYP Inhibitory Promiscuity | 0.5141 |
| Excretion | ||
| Toxicity | ||
| Human Ether-a-go-go-Related Gene Inhibition | Weak inhibitor | 0.9684 |
| Non-inhibitor | 0.8886 | |
| AMES Toxicity | Non AMES toxic | 0.9233 |
| Carcinogens | Non-carcinogens | 0.5609 |
| Fish Toxicity | High FHMT | 0.7527 |
| Tetrahymena Pyriformis Toxicity | High TPT | 0.9642 |
| Honey Bee Toxicity | High HBT | 0.5291 |
| Biodegradation | Not ready biodegradable | 0.9892 |
| Acute Oral Toxicity | III | 0.7824 |
| Carcinogenicity (Three-class) | Non-required | 0.6441 |
| Model | Value | Unit |
|---|---|---|
| Absorption | ||
| Aqueous solubility | -3.6177 | LogS |
| Caco-2 Permeability | 2.0508 | LogPapp, cm/s |
| Distribution | ||
| Metabolism | ||
| Excretion | ||
| Toxicity | ||
| Rat Acute Toxicity | 2.4363 | LD50, mol/kg |
| Fish Toxicity | 0.6985 | pLC50, mg/L |
| Tetrahymena Pyriformis Toxicity | 0.4828 | pIGC50, ug/L |
References
| Title | Journal | Date | Pubmed ID |
|---|---|---|---|
| Current and emerging pharmacotherapies for obesity in Australia. | Obes Res Clin Pract | 2017 Sep - Oct | 28818558 |
| Pharmacotherapy of Obesity: Clinical Trials to Clinical Practice. | Curr Diab Rep | 2017 May | 28378293 |
| An Update on Naltrexone/Bupropion Extended-Release in the Treatment of Obesity. | Expert Opin Pharmacother | 2016 Oct 4 | 27700187 |
| Stereoselective Glucuronidation of Bupropion Metabolites In Vitro and In Vivo. | Drug Metab Dispos | 2016 Apr | 26802129 |
| Drug treatment of obesity: current status and future prospects. | Eur J Intern Med | 2015 Mar | 25634851 |
| Modern obesity pharmacotherapy: weighing cardiovascular risk and benefit. | Clin Cardiol | 2014 Nov | 25223901 |
| Effect of uremic serum and uremic toxins on drug metabolism in human microsomes. | Regul Toxicol Pharmacol | 2014 Mar | 24184159 |
| New medications for obesity management: changing the landscape of obesitytreatment. | Curr Opin Endocrinol Diabetes Obes | 2013 Oct | 23974768 |
| Acute behavioural effects of bupropion and naltrexone, alone and in combination, in non-deprived male rats presented with palatable mash. | Psychopharmacology (Berl) | 2013 Jul | 23455599 |
| Effects of amylin and bupropion/naltrexone on food intake and body weight areinteractive in rodent models. | Eur J Pharmacol | 2013 Jan 5 | 23178527 |
| Behavioral characteristics and pharmacological manipulations of anicotine-entrainable circadian oscillator. | Chronobiol Int | 2013 Aug | 23697901 |
| Drug treatment of obesity. | Psychiatr Clin North Am | 2011 Dec | 22098810 |
| Gabapentin-induced delirium and dependence. | J Psychiatr Pract | 2009 Jul | 19625887 |
| Inhibition of dopamine and norepinephrine reuptake produces additive effects onenergy balance in lean and obese mice. | Neuropsychopharmacology | 2007 Apr | 16841072 |
| Drug-induced urticaria. | Expert Opin Drug Saf | 2004 Sep | 15335302 |
Targets
- General Function:
- Ligand-gated ion channel activity
- Specific Function:
- After binding acetylcholine, the AChR responds by an extensive change in conformation that affects all subunits and leads to opening of an ion-conducting channel across the plasma membrane.
- Gene Name:
- CHRNA3
- Uniprot ID:
- P32297
- Molecular Weight:
- 57479.54 Da
References
- Fryer JD, Lukas RJ: Noncompetitive functional inhibition at diverse, human nicotinic acetylcholine receptor subtypes by bupropion, phencyclidine, and ibogaine. J Pharmacol Exp Ther. 1999 Jan;288(1):88-92. [9862757 ]
- General Function:
- Norepinephrine:sodium symporter activity
- Specific Function:
- Amine transporter. Terminates the action of noradrenaline by its high affinity sodium-dependent reuptake into presynaptic terminals.
- Gene Name:
- SLC6A2
- Uniprot ID:
- P23975
- Molecular Weight:
- 69331.42 Da
- 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.
References
- Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]
- General Function:
- Ligand-gated ion channel activity
- Specific Function:
- After binding acetylcholine, the AChR responds by an extensive change in conformation that affects all subunits and leads to opening of an ion-conducting channel across the plasma membrane permeable to sodium ions.
- Gene Name:
- CHRNA4
- Uniprot ID:
- P43681
- Molecular Weight:
- 69956.47 Da
References
- Carroll FI, Blough BE, Mascarella SW, Navarro HA, Eaton JB, Lukas RJ, Damaj MI: Synthesis and biological evaluation of bupropion analogues as potential pharmacotherapies for smoking cessation. J Med Chem. 2010 Mar 11;53(5):2204-14. doi: 10.1021/jm9017465. [20158204 ]
- General Function:
- G-protein coupled acetylcholine receptor activity
- Specific Function:
- The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is adenylate cyclase inhibition. Signaling promotes phospholipase C activity, leading to the release of inositol trisphosphate (IP3); this then triggers calcium ion release into the cytosol.
- Gene Name:
- CHRM2
- Uniprot ID:
- P08172
- Molecular Weight:
- 51714.605 Da
References
- Cusack B, Nelson A, Richelson E: Binding of antidepressants to human brain receptors: focus on newer generation compounds. Psychopharmacology (Berl). 1994 May;114(4):559-65. [7855217 ]
- General Function:
- Serotonin receptor activity
- Specific Function:
- G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various drugs and psychoactive substances, including ergot alkaloid derivatives, 1-2,5,-dimethoxy-4-iodophenyl-2-aminopropane (DOI) and lysergic acid diethylamide (LSD). Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors. Beta-arrestin family members inhibit signaling via G proteins and mediate activation of alternative signaling pathways. Signaling activates a phosphatidylinositol-calcium second messenger system that modulates the activity of phosphatidylinositol 3-kinase and down-stream signaling cascades and promotes the release of Ca(2+) ions from intracellular stores. Regulates neuronal activity via the activation of short transient receptor potential calcium channels in the brain, and thereby modulates the activation of pro-opiomelacortin neurons and the release of CRH that then regulates the release of corticosterone. Plays a role in the regulation of appetite and eating behavior, responses to anxiogenic stimuli and stress. Plays a role in insulin sensitivity and glucose homeostasis.
- Gene Name:
- HTR2C
- Uniprot ID:
- P28335
- Molecular Weight:
- 51820.705 Da
References
- Cusack B, Nelson A, Richelson E: Binding of antidepressants to human brain receptors: focus on newer generation compounds. Psychopharmacology (Berl). 1994 May;114(4):559-65. [7855217 ]
- General Function:
- Thioesterase binding
- Specific Function:
- Alpha-2 adrenergic receptors mediate the catecholamine-induced inhibition of adenylate cyclase through the action of G proteins. The rank order of potency for agonists of this receptor is oxymetazoline > clonidine > epinephrine > norepinephrine > phenylephrine > dopamine > p-synephrine > p-tyramine > serotonin = p-octopamine. For antagonists, the rank order is yohimbine > phentolamine = mianserine > chlorpromazine = spiperone = prazosin > propanolol > alprenolol = pindolol.
- Gene Name:
- ADRA2A
- Uniprot ID:
- P08913
- Molecular Weight:
- 48956.275 Da
References
- Cusack B, Nelson A, Richelson E: Binding of antidepressants to human brain receptors: focus on newer generation compounds. Psychopharmacology (Berl). 1994 May;114(4):559-65. [7855217 ]
- General Function:
- Histamine receptor activity
- Specific Function:
- In peripheral tissues, the H1 subclass of histamine receptors mediates the contraction of smooth muscles, increase in capillary permeability due to contraction of terminal venules, and catecholamine release from adrenal medulla, as well as mediating neurotransmission in the central nervous system.
- Gene Name:
- HRH1
- Uniprot ID:
- P35367
- Molecular Weight:
- 55783.61 Da
References
- Cusack B, Nelson A, Richelson E: Binding of antidepressants to human brain receptors: focus on newer generation compounds. Psychopharmacology (Berl). 1994 May;114(4):559-65. [7855217 ]
- General Function:
- Phosphatidylinositol phospholipase c activity
- Specific Function:
- The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is Pi turnover.
- Gene Name:
- CHRM1
- Uniprot ID:
- P11229
- Molecular Weight:
- 51420.375 Da
References
- Stanton T, Bolden-Watson C, Cusack B, Richelson E: Antagonism of the five cloned human muscarinic cholinergic receptors expressed in CHO-K1 cells by antidepressants and antihistaminics. Biochem Pharmacol. 1993 Jun 9;45(11):2352-4. [8100134 ]
- General Function:
- Toxic substance binding
- Specific Function:
- After binding acetylcholine, the AChR responds by an extensive change in conformation that affects all subunits and leads to opening of an ion-conducting channel across the plasma membrane. The channel is blocked by alpha-bungarotoxin.
- Gene Name:
- CHRNA7
- Uniprot ID:
- P36544
- Molecular Weight:
- 56448.925 Da
References
- Jensen AA, Frolund B, Liljefors T, Krogsgaard-Larsen P: Neuronal nicotinic acetylcholine receptors: structural revelations, target identifications, and therapeutic inspirations. J Med Chem. 2005 Jul 28;48(15):4705-45. [16033252 ]
- General Function:
- Guanyl-nucleotide exchange factor activity
- Specific Function:
- The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is inhibition of adenylate cyclase.
- Gene Name:
- CHRM4
- Uniprot ID:
- P08173
- Molecular Weight:
- 53048.65 Da
References
- Stanton T, Bolden-Watson C, Cusack B, Richelson E: Antagonism of the five cloned human muscarinic cholinergic receptors expressed in CHO-K1 cells by antidepressants and antihistaminics. Biochem Pharmacol. 1993 Jun 9;45(11):2352-4. [8100134 ]
- General Function:
- Serotonin receptor activity
- Specific Function:
- G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various drugs and psychoactive substances. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase. Beta-arrestin family members inhibit signaling via G proteins and mediate activation of alternative signaling pathways. Signaling inhibits adenylate cyclase activity and activates a phosphatidylinositol-calcium second messenger system that regulates the release of Ca(2+) ions from intracellular stores. Plays a role in the regulation of 5-hydroxytryptamine release and in the regulation of dopamine and 5-hydroxytryptamine metabolism. Plays a role in the regulation of dopamine and 5-hydroxytryptamine levels in the brain, and thereby affects neural activity, mood and behavior. Plays a role in the response to anxiogenic stimuli.
- Gene Name:
- HTR1A
- Uniprot ID:
- P08908
- Molecular Weight:
- 46106.335 Da
References
- Cusack B, Nelson A, Richelson E: Binding of antidepressants to human brain receptors: focus on newer generation compounds. Psychopharmacology (Berl). 1994 May;114(4):559-65. [7855217 ]
- General Function:
- Receptor activity
- Specific Function:
- The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is Pi turnover.
- Gene Name:
- CHRM3
- Uniprot ID:
- P20309
- Molecular Weight:
- 66127.445 Da
References
- Stanton T, Bolden-Watson C, Cusack B, Richelson E: Antagonism of the five cloned human muscarinic cholinergic receptors expressed in CHO-K1 cells by antidepressants and antihistaminics. Biochem Pharmacol. 1993 Jun 9;45(11):2352-4. [8100134 ]
- General Function:
- Monoamine transmembrane transporter activity
- Specific Function:
- Amine transporter. Terminates the action of dopamine by its high affinity sodium-dependent reuptake into presynaptic terminals.
- Gene Name:
- SLC6A3
- Uniprot ID:
- Q01959
- Molecular Weight:
- 68494.255 Da
- 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.
References
- Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]
- General Function:
- Serotonin:sodium symporter activity
- Specific Function:
- Serotonin transporter whose primary function in the central nervous system involves the regulation of serotonergic signaling via transport of serotonin molecules from the synaptic cleft back into the pre-synaptic terminal for re-utilization. Plays a key role in mediating regulation of the availability of serotonin to other receptors of serotonergic systems. Terminates the action of serotonin and recycles it in a sodium-dependent manner.
- Gene Name:
- SLC6A4
- Uniprot ID:
- P31645
- Molecular Weight:
- 70324.165 Da
References
- Tatsumi M, Groshan K, Blakely RD, Richelson E: Pharmacological profile of antidepressants and related compounds at human monoamine transporters. Eur J Pharmacol. 1997 Dec 11;340(2-3):249-58. [9537821 ]