Bupropion
Systematic (IUPAC) name
(±)-2-(tert-butylamino)-1-(3-chlorophenyl)propan-1-one
Identifiers
CAS number	34841-39-9
ATC code	N07BA02
PubChem	444
DrugBank	APRD00621
Chemical data
Formula	C13H18ClNO
Mol. mass	239. IUPAC Nomenclature is a system of naming Chemical compounds and of describing the science of Chemistry in general CAS registry numbers are unique numerical identifiers for Chemical compounds Polymers biological sequences mixtures and Alloys They are also referred to The Anatomical Therapeutic Chemical Classification System is used for the classification of drugs It is controlled by the WHO Collaborating Centre for Drug ATC code N07 is a section of the Anatomical Therapeutic Chemical Classification System. PubChem is a Database of chemical Molecules The system is maintained by the National Center for Biotechnology Information (NCBI a component The DrugBank database available at the University of Alberta is a unique Bioinformatics and Cheminformatics resource that combines detailed drug (i A chemical formula is a way of expressing information about the Atoms that constitute a particular Chemical compound, and how the relationship between those atoms changes Carbon (kɑɹbən is a Chemical element with the symbol C and its Atomic number is 6 Hydrogen (ˈhaɪdrədʒən is the Chemical element with Atomic number 1 Chlorine (ˈklɔriːn from the Greek word 'χλωρóς' ( khlôros, meaning 'pale green' is the Chemical element with Atomic number 17 and Nitrogen (ˈnaɪtɹəʤɪn is a Chemical element that has the symbol N and Atomic number 7 and Atomic weight 14 Oxygen (from the Greek roots ὀξύς (oxys (acid literally "sharp" from the taste of acids and -γενής (-genēs (producer literally begetteris the The molecular mass (abbreviated m of a substance, more commonly referred to as molecular weight and abbreviated as MW, is the Mass of one 74 g/mol
SMILES	eMolecules & PubChem
Pharmacokinetic data
Bioavailability	5 to 20% in animals; no studies in humans
Metabolism	Hepatic—important CYP2B6 and 2D6 involvement
Half life	20 hours
Excretion	Renal (87%), fecal (10%)
Therapeutic considerations
Pregnancy cat.	B2(AU) C(US)
Legal status	POM(UK) ℞-only(US)
Routes	Oral

Bupropion (INN; previously known as amfebutamone,^[1] Wellbutrin, Zyban) is an atypical antidepressant that acts as a norepinephrine and dopamine reuptake inhibitor, and nicotinic antagonist. In Pharmacology, bioavailability is used to describe the fraction of an administered Dose of unchanged drug that reaches the Systemic circulation, one of Drug metabolism is the Metabolism of drugs, their Biochemical modification or degradation usually through specialized enzymatic systems The liver is a vital organ in the human body and is present in Vertebrates and some other animals CYP2B6 is a member of the Cytochrome P450 group of enzymes Along with CYP2A6, it is involved with metabolizing Nicotine, along with many other substances Cytochrome P450 2D6 (CYP2D6 a member of the Cytochrome P450 mixed-function oxidase system is one of the most important enzymes involved in the metabolism of Xenobiotics The biological half-life of a substance is the time it takes for a substance (drug radioactive nuclide or other to lose half of its pharmacologic physiologic or radiologic activity Excretion is the process of eliminating waste products of Metabolism and other non-useful materials The kidneys are complicated organs that have numerous biological roles The pregnancy category of a pharmaceutical agent is an assessment of the risk of fetal injury due to the pharmaceutical if it is used as directed by the mother during For a topic outline on this subject see List of basic Australia topics. The United States of America —commonly referred to as the The regulation of therapeutic goods, that is drugs and therapeutic devices, varies by jurisdiction A prescription drug is a licensed medicine that is regulated by legislation to require a prescription before it can be obtained The United Kingdom of Great Britain and Northern Ireland, commonly known as the United Kingdom, the UK or Britain,is a Sovereign state located A prescription drug is a licensed medicine that is regulated by legislation to require a prescription before it can be obtained The United States of America —commonly referred to as the In Pharmacology and Toxicology, a route An International Nonproprietary Name ( INN; also known as rINN, for recommended International Nonproprietary Name or pINN for proposed An antidepressant is a Psychiatric medication used for alleviating major depression or Dysthymia ('milder' depression Norepinephrine reuptake inhibitors ( NRIs) also known as noradrenaline reuptake inhibitors ( NARIs) are compounds that elevate the extracellular level of Dopamine Reuptake Inhibitors ( DARI) Dopamine Uptake Inhibitors, Dopamine Transporter Inhibitors are compounds that inhibit the Reuptake of extracellular A nicotinic antagonist is a type of Anticholinergic which inhibits the action at Nicotinic acetylcholine receptors These compounds are mainly used for peripheral muscle ^[2][3] Bupropion belongs to the chemical class of aminoketones and is similar in structure to the stimulant cathinone, to the anorectic diethylpropion, and to phenethylamines in general. Stimulant drugs are Drugs that temporarily increase alertness and awareness Cathinone ( β - keto[[amphetamine]] is a Monoamine Alkaloid found in the Shrub Catha edulis ( Khat Note "Anorectic" is also a term for an anorexic person a person suffering from Anorexia nervosa Anorectics, anorexigenics Diethylcathinone (also called Diethylpropion and Amfepramone) is a Sympathomimetic Stimulant drug marketed as an appetite Phenethylamine, or β -phenylethylamine or 2-phenylethylamine is an Alkaloid and Monoamine.

Initially researched and marketed as an antidepressant, bupropion was subsequently found to be effective as a smoking cessation aid. An antidepressant is a Psychiatric medication used for alleviating major depression or Dysthymia ('milder' depression Smoking cessation is the effort to stop smoking Tobacco products In 2007 it was the fourth-most prescribed antidepressant in the United States retail market, with 20. 184 million retail prescriptions. ^[4]

Bupropion lowers seizure threshold and its potential to cause seizures was widely publicized. An epileptic seizure is caused by excessive and/or hypersynchronous electrical Neuronal activity and is usually self-limiting However, at the recommended dose the risk of seizures is comparable to that observed for other antidepressants. Bupropion is an effective antidepressant on its own but it is particularly popular as an add-on medication in the cases of incomplete response to the first-line SSRI antidepressant. Selective serotonin reuptake inhibitors ( SSRIs) are a class of Antidepressants used in the treatment of depression, Anxiety disorders In contrast to many psychiatric drugs, including nearly all antidepressants, bupropion does not cause weight gain or sexual dysfunction. Sexual dysfunction or sexual malfunction (see also Sexual function) is difficulty during any stage of the Sexual act (which includes desire,

Contents 1 History 2 Therapeutic uses 2.1 Depression 2.2 Smoking cessation 2.3 Sexual dysfunction 2.4 Obesity 2.5 Attention-deficit hyperactivity disorder 2.6 Other uses 3 Contraindications 3.1 Risk of suicide 4 Adverse effects 5 Overdose 6 Mechanism of action 7 Pharmacokinetics 8 Interactions 9 Availability and dose forms 10 Abuse liability 11 References 12 External links

History

Bupropion was invented by Nariman Mehta of Burroughs Wellcome (now GlaxoSmithKline) in 1969, and the US patent for it was granted in 1974. GlaxoSmithKline plc () is a United Kingdom -based pharmaceutical, biological and Healthcare Company. ^[5] It was approved by the United States Food and Drug Administration (FDA) as an antidepressant on December 30, 1985 and marketed under the name Wellbutrin. ^[6] However, a significant incidence of seizures at the originally recommended dosage (400–600 mg) caused the withdrawal of the drug in 1986. An epileptic seizure is caused by excessive and/or hypersynchronous electrical Neuronal activity and is usually self-limiting Subsequently, the risk of seizures was found to be highly dose-dependent, and bupropion was re-introduced to the market in 1989 with a maximum recommended dose of 450 mg/day.

In 1996, the FDA approved a sustained-release formulation of bupropion called Wellbutrin SR, intended to be taken twice a day (as compared to three times a day for immediate-release Wellbutrin). Sustained-release ( SR) extended-release ( ER, XR, or XL) time-release or timed-release, controlled-release ^[7] In 2003 the FDA approved another sustained-release formulation called Wellbutrin XL, intended for once-daily dosing. Wellbutrin SR and XL are available in the United States and Canada in generic form. A generic drug (generic drugs short generics is a drug which is produced and distributed without Patent protection In 1997, bupropion was approved by the FDA for use as a smoking cessation aid under the name Zyban. Smoking cessation is the effort to stop smoking Tobacco products ^[7] In 2006, Wellbutrin XL was similarly approved as a treatment for seasonal affective disorder. Seasonal affective disorder ( SAD) also known as winter depression, is a Mood disorder in which people who have normal mental health throughout most of the year experience ^[8]

Therapeutic uses

Depression

Placebo-controlled double-blind clinical studies have confirmed the efficacy of bupropion for clinical depression. Placebo is a substance or procedure a patient accepts as medicine or therapy but which has no specific therapeutic activity The blind method is a part of the Scientific method, used to prevent research outcomes from being influenced by either the Placebo effect or the Observer In health care clinical trials are conducted to allow safety and Efficacy data to be collected for new drugs or devices Major depressive disorder, also known as major depression, unipolar depression, unipolar disorder, clinical depression, or simply depression ^[9] Comparative clinical studies demonstrated the equivalency of bupropion and sertraline (Zoloft), fluoxetine (Prozac), paroxetine (Paxil)^[10] and escitalopram (Lexapro)^[11] as antidepressants. Paroxetine (trade names Seroxat, Paxil, Parotin, Aropax, Xetanor, ParoMerck, Rexetin) is a Selective serotonin Escitalopram (trade names Lexapro, Cipralex) is the pure (S Enantiomer of Citalopram and is a Selective serotonin reuptake inhibitor A significantly higher remission rate with bupropion treatment than for venlafaxine (Effexor) was observed in a recent study. Remission is the state of absence of Disease activity in patients with known Chronic illness. Venlafaxine (Effexor Efexor is an Antidepressant of the Serotonin-norepinephrine reuptake inhibitor (SNRI class first introduced by Wyeth in 1993 ^[12] Unlike all other antidepressants, except mirtazapine (Remeron), maprotiline (Ludiomil) and tianeptine (Stablon), bupropion does not cause sexual dysfunction and the occurrence of sexual side effects is not different from placebo. Mirtazapine is an Antidepressant introduced by Organon International in 1994 used for the treatment of moderate to severe depression. Maprotiline (sold as Deprilept, Ludiomil, Psymion) is a Tetracyclic antidepressant. Tianeptine ( INN) (Stablon Coaxil Tatinol is described as a Selective serotonin reuptake enhancer ( SSRE) ^[13][14] Bupropion treatment is not associated with weight gain; on the contrary, at the end of every study comparing bupropion with placebo or other antidepressants the bupropion group had a lower average weight. ^[15] Bupropion is more effective than SSRIs at improving symptoms of hypersomnia and fatigue in depressed patients. Selective serotonin reuptake inhibitors ( SSRIs) are a class of Antidepressants used in the treatment of depression, Anxiety disorders Hypersomnia is excessive amount of sleepiness. Description Hypersomnia is characterized by reoccuring episodes of Excessive daytime sleepiness ^[16]

According to several surveys, the augmentation of a prescribed SSRI with bupropion is the preferred strategy among clinicians when the patient does not respond to the SSRI. Selective serotonin reuptake inhibitors ( SSRIs) are a class of Antidepressants used in the treatment of depression, Anxiety disorders ^[17] For example, the combination of bupropion and citalopram (Celexa) was observed to be more effective than switching to another antidepressant. Citalopram is an Antidepressant drug used to treat major depression associated with Mood disorders It is also used on occasion in the treatment The addition of bupropion to an SSRI (primarily fluoxetine or sertraline) resulted in a significant improvement in 70–80% of patients who had an incomplete response to the first-line antidepressant. ^[18][19] Bupropion improved ratings of "energy", which had decreased under the influence of the SSRI; also noted were improvements of mood and motivation, and some improvement of cognitive and sexual functions. Sleep quality and anxiety ratings in most cases were unchanged. ^[19] In the STAR*D study, the patients who did not respond to citalopram (Celexa) were randomly assigned to augmentation by bupropion or buspirone (Buspar). Citalopram is an Antidepressant drug used to treat major depression associated with Mood disorders It is also used on occasion in the treatment Buspirone (brand-names Ansial, Ansiced, Anxiron, Axoren, Bespar, BuSpar, Buspimen, Buspinol, Approximately 30% of subjects in both groups achieved a remission. However, bupropion augmentation gave better results based on the patients' self-ratings and was much better tolerated. The authors observed that "these findings reveal a consistently more favorable outcome with sustained-release bupropion than with buspirone augmentation of citalopram. "^[20] The same study indicated a possibility of higher remission rate when the non-responders to citalopram received bupropion augmentation rather than were switched to bupropion (30% vs. 20%). ^[21]

Smoking cessation

Bupropion reduces the severity of nicotine cravings and withdrawal symptoms. Nicotine is an Alkaloid found in the Nightshade family of plants ( Solanaceae) which constitutes approximately 0 Withdrawal, also known as withdrawal/abstinence syndrome, refers to the characteristic signs and symptoms that appear when a drug that causes Physical dependence is After a seven-week treatment, 27% of subjects who received bupropion reported that an urge to smoke was a problem, versus 56% of those who received placebo. Placebo is a substance or procedure a patient accepts as medicine or therapy but which has no specific therapeutic activity In the same study, 21% of the bupropion group reported mood swings, versus 32% of the placebo group. ^[22] The bupropion treatment course lasts for seven to twelve weeks, with the patient halting the use of tobacco about ten days into the course. The efficacy of bupropion is similar to that of nicotine replacement therapy. Bupropion approximately doubles the chance of quitting smoking successfully after three months. One year after the treatment, the odds of sustaining smoking cessation are still 1. 5 times higher in the bupropion group than in the placebo group. ^[23] The combination of bupropion and nicotine appears not to further increase the cessation rate. In a direct comparison, varenicline (Chantix) showed superior efficacy: after one year, the rate of continuous abstinence was 10% for placebo, 15% for bupropion, and 23% for varenicline. Varenicline (trade name Chantix in the USA and Champix in Europe and other countries marketed by Pfizer, usually in the form of varenicline tartrate ^[24] Bupropion slows the weight gain that often occurs in the first weeks after quitting smoking (after seven weeks, the placebo group had an average 2. 7 kg increase in weight, versus 1. 5 kg for the bupropion group). With time, however, this effect becomes negligible (after 26 weeks, both groups recorded an average 4. 8 kg weight gain). ^[22]

Sexual dysfunction

According to a survey, bupropion is the drug of choice among psychiatrists for the treatment of SSRI-induced sexual dysfunction, although it is not an FDA-approved indication. 36 percent of responding psychiatrists preferred switching patients with SSRI-induced sexual dysfunction to bupropion; however, 43 percent favored the augmentation of the current medication with bupropion. ^[25] There are studies demonstrating the efficacy of both approaches; improvement of the desire and orgasm components of sexual function were the most often noted. For the augmentation approach, the addition of at least 200 mg/day of bupropion to the SSRI regimen may be necessary to achieve an improvement since the addition of 150 mg/day of bupropion did not produce a statistically significant difference from placebo. ^{[26][27][28][29][30][31]}

Several studies have indicated that bupropion also relieves sexual dysfunction in people who do not have depression. In a mixed-gender double-blind study, 63% of subjects on a 12-week course of bupropion rated their condition as improved or much improved, versus 3% of subjects on placebo. ^[32] Two studies, one of which was placebo-controlled, demonstrated the efficacy of bupropion for women with hypoactive sexual desire,^[33][34] resulting in significant improvement of arousal, orgasm and overall satisfaction. Bupropion also showed promise as a treatment for sexual dysfunction caused by chemotherapy for breast cancer^[35] and for orgasmic dysfunction. Chemotherapy, in its most general sense refers to treatment of disease by chemicals that kill cells specifically those of micro-organisms or Cancer. ^[36] As with the treatment of SSRI-induced sexual disorder, a higher dose of bupropion (300 mg) may be necessary: a randomized study employing a lower dose (150 mg) failed to find a significant difference between bupropion, sexual therapy or combined treatment. ^[37] Bupropion does not affect any measures of sexual functioning in healthy men. ^[38]

Obesity

A recent meta-analysis of anti-obesity medications pooled the results of three double-blind, placebo-controlled trials of bupropion. In Statistics, a meta-analysis combines the results of several studies that address a set of related research hypotheses Anti-obesity drugs or weight loss drugs refer to all pharmacological agents that reduce or control weight. It confirmed the efficacy of bupropion given at 400 mg per day for treating obesity. Over a period of 6 to 12 months, weight loss in the bupropion group (4. 4 kg) was significantly greater than in the placebo group (1. 7 kg). The same review found the differences in weight loss between bupropion and other established weight-loss medications, such as sibutramine, orlistat and diethylpropion, to be statistically insignificant. Sibutramine (trade name Meridia in the US and Canada Reductil in Europe and most other countries usually as sibutramine hydrochloride monohydrate is an orally Orlistat (marketed under the trade name Xenical by Roche; or over-the-counter as alli by GlaxoSmithKline (ˈælaɪ like the English Diethylcathinone (also called Diethylpropion and Amfepramone) is a Sympathomimetic Stimulant drug marketed as an appetite ^[39]

Attention-deficit hyperactivity disorder

Although attention-deficit hyperactivity disorder (ADHD) is not an approved indication, bupropion was found to be effective for adult ADHD. Attention-Deficit Hyperactivity Disorder (ADHD is a neurobehavioral developmental disorder affecting about 3-5% of the world's population ^[40] There have been many positive case studies and other uncontrolled clinical studies of bupropion for ADHD in minors. ^[41] However, in the largest to date double-blind study, which was conducted by GlaxoSmithKline, the results were inconclusive. Aggression and hyperactivity as rated by the children's teachers were significantly improved in comparison to placebo; in contrast, parents and clinicians could not distinguish between the effects of bupropion and placebo. ^[41] The 2007 guideline on the ADHD treatment from American Academy of Child and Adolescent Psychiatry notes that the evidence for bupropion is "far weaker" than for the FDA-approved treatments. Its effect may also be "considerably less than of the approved agents. . . Thus it may be prudent for the clinician to recommend a trial of behavior therapy at this point, before moving to these second-line agents. "^[42] Similarly, the 2006 guideline from the Texas Department of State Health Services recommends considering bupropion or a tricyclic antidepressant as a fourth-line treatment after trying two different stimulants and atomoxetine (Strattera). Tricyclic antidepressants (abbreviation TCAs) are a class of Antidepressant drugs first used in the 1950s Atomoxetine is a non- Stimulant drug approved for the treatment of Attention-deficit hyperactivity disorder (ADHD ^[43][44]

A study of prophylactic bupropion for the prevention of smoking among teenagers with ADHD yielded unexpected results. Attention-Deficit Hyperactivity Disorder (ADHD is a neurobehavioral developmental disorder affecting about 3-5% of the world's population The teenagers taking bupropion were twice more likely (close to statistical significance) to begin smoking than the teenagers in the placebo group. At the same time, the sub-group of patients taking stimulants in addition to bupropion or placebo had a five times lower risk of smoking initiation. ^[45]

Other uses

Bupropion is used for the prevention of seasonal affective disorder,^[46] and has been approved by the FDA for the latter indication. Seasonal affective disorder ( SAD) also known as winter depression, is a Mood disorder in which people who have normal mental health throughout most of the year experience ^[47] There is considerable disagreement regarding whether the addition of an antidepressant, including bupropion, to a mood stabilizer in patients with bipolar depression is useful. This article refers to the medication For other uses see Stabilizer. ^[48][49][50]

No properly controlled double-blind studies of bupropion for Parkinson's disease have been conducted. Parkinson's disease (also known as Parkinson disease or PD) is a degenerative disorder of the Central nervous system that often impairs the sufferer's A small 1984 study funded by bupropion's manufacturer found that addition of bupropion to carbidopa or levodopa improved Parkinson's symptoms in ten out of twenty patients; however, the side effects, particularly nausea and vomiting, were frequent. Carbidopa (MK-486 tradename Lodosyn) is a drug given to people with Parkinson's disease in order to inhibit peripheral Metabolism of Levodopa ^[51] The American Psychiatric Association notes that, "there is no evidence favoring any particular antidepressant medication from the standpoint of therapeutic efficacy in patients with Parkinson’s disease complicated by major depressive disorder. The American Psychiatric Association (APA is the main Professional organization of Psychiatrists and trainee psychiatrists in the United States, and the "^[52]

Contraindications

GlaxoSmithKline advises that bupropion should not be prescribed to individuals with epilepsy or other conditions that lower the seizure threshold, such as alcohol or benzodiazepine discontinuation, anorexia nervosa, bulimia, or active brain tumors. Epilepsy is a common chronic Neurological disorder that is characterized by recurrent unprovoked seizures. An epileptic seizure is caused by excessive and/or hypersynchronous electrical Neuronal activity and is usually self-limiting The benzodiazepines (pronounced, often abbreviated to "benzos") are a class of Psychoactive drugs with varying Hypnotic Anorexia Nervosa is a psychiatric Diagnosis that describes an Eating disorder characterized by low Body weight and Body image distortion Bulimia nervosa is an Eating disorder characterized by recurrent Binge eating, followed by compensatory behaviors referred to as "purging" A brain tumor is any intracranial Tumor created by abnormal and uncontrolled cell division, normally either in the Brain itself ( Neurons It should be avoided in individuals who are also taking MAO inhibitors (MAOIs). Monoamine oxidase inhibitors ( MAOIs) are a class of powerful antidepressant drugs prescribed for the treatment of depression. When switching from MAOIs to bupropion, it is important to include a washout period of about two weeks between the medications. ^[53] The prescribing information approved by the FDA recommends that caution should be exercised when treating patients with liver damage, severe kidney disease, and severe hypertension, as well as in pediatric patients, adolescents and young adults due to the increased risk of suicidal ideation. Nephrology (from Greek nephros, " Kidney " and λόγος Logos, "speech" lit Hypertension, also referred to as high blood pressure, HTN or HPN, is a medical condition in which the Blood pressure is chronically elevated ^[53]

According to a retrospective case series published in 1993, bupropion treatment may exacerbate tics in children with co-occurring ADHD and Tourette syndrome. Retrospective (from Latin retrospectare, "look back" generally means to take a look back at events that already have taken place A case series (also known as a clinical series) is a medical research study that tracks patients with a known exposure given similar treatment or examines their medical records A tic is a sudden repetitive nonrhythmic stereotyped motor movement or vocalization involving discrete muscle groups In Medicine, comorbidity (literally "additional Morbidity " is either * The presence of one or more disorders (or diseases in addition to Attention-Deficit Hyperactivity Disorder (ADHD is a neurobehavioral developmental disorder affecting about 3-5% of the world's population Tourette syndrome (also called Tourette's syndrome, Tourette's disorder, Gilles de la Tourette syndrome, GTS or more commonly simply Tourette's ^[54] No further research of this side effect has been conducted.

Risk of suicide

The FDA requires all antidepressants, including bupropion, to carry a black box warning stating that antidepressants may increase the risk of suicide in persons younger than 25. In the United States, a black box warning (also sometimes called a black label warning or boxed warning) is a type of warning that appears on the Package This warning is based on a statistical analysis conducted by the FDA which found a 2-fold increase of the suicidal ideation and behavior in children and adolescents, and 1. 5-fold increase of suicidality in the 18–24 age group. ^[55]

Suicidal ideation and behavior in clinical trials are rare. For the above analysis, the FDA combined the results of 295 trials of 11 antidepressants for psychiatric indications in order to obtain statistically significant results. In Statistics, a result is called statistically significant if it is unlikely to have occurred by Chance. Considered separately, bupropion and nine other antidepressants were not statistically different from placebo. Only fluoxetine caused a significant decrease in suicidal ideation. ^[55]

Suicidal behavior is even less likely when bupropion is prescribed for smoking cessation. According to a Cochrane Database review, there have been four suicides per one million prescriptions and one case of suicidal ideation per ten thousand prescriptions of bupropion for smoking cessation in the UK. The Cochrane Library is a collection of databases in medicine and other healthcare specialties provided by the Cochrane Collaboration and other organisations The review concludes, "Although some suicides and deaths while taking bupropion have been reported, thus far there is insufficient evidence to suggest they were caused by bupropion. "^[56]

Adverse effects

The common adverse effects associated with 12-hour sustained-release bupropion (with the greatest difference from placebo) are dry mouth, nausea, insomnia, tremor, excessive sweating and tinnitus. An adverse drug reaction (abbreviated ADR) or adverse drug event (abbreviated ADE) is an expression that describes the unwanted negative consequences Xerostomia is the medical term for a dry mouth due to a lack of Saliva. Nausea ( Latin: Nausea, Greek:, " Sea-sickness " also called wamble) is the sensation of unease and discomfort Insomnia is a symptom of a sleeping disorder characterized by persistent difficulty falling asleep or staying asleep despite the opportunity Tremor is an unintentional somewhat rhythmic muscle movement involving to-and-from movements (oscillations of one or more parts of the body Tinnitus (tɪˈnaɪtəs or /ˈtɪnɪtəs/ from the Latin word for " Ringing " is the perception of sound within the human ear in the absence of corresponding Those that most often resulted in interruption of the treatment in the same trial were rash (2. 4%) and nausea (0. 8%). The development of mild to moderate skin rashes is associated with sensitivity to dye components within the pill coating. A rash is a change of the Skin which affects its color appearance or Texture. This can often be alleviated simply by prescribing a differently colored pill. ^[53]

Seizure is the most controversial side effect of bupropion, and was responsible for its initial withdrawal from the market. An epileptic seizure is caused by excessive and/or hypersynchronous electrical Neuronal activity and is usually self-limiting The risk of seizure is highly dose-dependent: 0. 1% at 100–300 mg of bupropion, 0. 4% at 300–450 mg, and 2% at 600 mg. For comparison, the incidence of the first unprovoked seizure in the general population is 0. 07–0. 09%. The risk of seizure for other antidepressants is as follows: 0. 1–0. 6% for imipramine, depending on dosage; 0–0. Imipramine (sold as Antideprin, Deprenil, Deprimin, Deprinol, Depsonil, Dynaprin, Eupramin, Imipramil 06% for amitriptyline, depending on dosage; 0. Amitriptyline (or Amitryptyline) hydrochloride (sold as Elavil Tryptanol Endep Elatrol Tryptizol Trepiline Laroxyl Saroten is a Tricyclic antidepressant 5% for clomipramine; 0. Clomipramine (brand-name Anafranil) is a Tricyclic antidepressant. 4% for maprotiline; and 0. Maprotiline (sold as Deprilept, Ludiomil, Psymion) is a Tetracyclic antidepressant. 2% for fluoxetine and fluvoxamine. Fluvoxamine ( Luvox) is an Antidepressant which functions as a Selective serotonin reuptake inhibitor. ^[57] Experiments on mice indicate that increased susceptibility to seizure is a general side effect of chronically using antidepressants that inhibit norepinephrine transporter, such as imipramine, desipramine and reboxetine. Imipramine (sold as Antideprin, Deprenil, Deprimin, Deprinol, Depsonil, Dynaprin, Eupramin, Imipramil Desipramine is a Tricyclic antidepressant (TCA that inhibits the reuptake of Norepinephrine. Reboxetine is an Antidepressant drug used in the treatment of Clinical depression, Panic disorder and ADD/ADHD, developed by Pharmacia (now ^[58] Clinical depression itself was reported to increase the occurrence of seizures two-to-seven-fold compared with the general population; in this light, the above statistics could indicate that low to moderate doses of antidepressants, including bupropion, may actually have an anti-convulsive action. ^[59]

There is evidence of several neuropsychiatric symptoms associated with bupropion in patients with depression, including delusions, hallucinations, psychosis, concentration disturbance, paranoia, and confusion. A hallucination, in the broadest sense is a Perception in the absence of a stimulus. Psychosis (from the Greek ψυχή "psyche" for mind or soul and -οσις "-osis" for abnormal condition with adjective psychotic Paranoia is a disturbed thought process characterized by excessive Anxiety or Fear, often to the point of Irrationality and Delusion. In some cases, these symptoms are reduced or eliminated by decreasing the dose or ceasing treatment. The prescribing information notes that "it is generally believed (though not established in controlled trials)" that, should an episode of depression actually be the first presentation of bipolar disorder, treating it with antidepressants, including bupropion, may precipitate a manic episode. ^[53] More recent data indicate that the addition of newer antidepressants, including bupropion, to a mood stabilizer does not cause the switch to mania more often than the addition of placebo. This article refers to the medication For other uses see Stabilizer. ^[49] Moreover, when added to a mood stabilizer, bupropion and sertraline had a twice lower switch risk than venlafaxine. ^[60]

The prescribing information notes that hypertension, sometimes severe, was observed in some patients, both with and without pre-existing hypertension. Hypertension, also referred to as high blood pressure, HTN or HPN, is a medical condition in which the Blood pressure is chronically elevated The frequency of this adverse effect was under 1% and not significantly higher than that found with placebo. ^[53] In a group of cardiac patients with depression, high doses of bupropion (400–500 mg/day) caused a rise in supine blood pressure but had no effect on pulse rate. In Grammar a supine is a form of Verbal noun used in some languages ^[61] No statistically significant changes in blood pressure or heart rate occurred in patients with or without heart conditions at a lower dose of 300 mg/day. ^[62] In a study of bupropion for ADHD, a rise of systolic blood pressure by 6 mm Hg and of heart rate by 7 beats per minute (both statistically significant) were observed. Attention-Deficit Hyperactivity Disorder (ADHD is a neurobehavioral developmental disorder affecting about 3-5% of the world's population Systole (ˈsɪstɒli rhymes with "fiscally" is the contraction of Heart chambers driving blood out of the chambers ^[63] A study of smokers hospitalized for heart disease found a 1. 5-fold increase (close to being statistically significant) in subsequent cardiovascular events in the bupropion group, compared with the placebo group, but found no difference in blood pressure. ^[64] Although the cardiovascular side effects of bupropion appear to be mild, it cannot be recommended for patients with heart disease, since the safety comparison with SSRIs (such as sertraline and fluoxetine, which may have a preventative effect after a myocardial infarction^[65]) is not in its favor. Myocardial infarction ( MI or AMI for acute myocardial infarction) also known as a heart attack, occurs when the blood supply

In the UK, more than 7,600 reports of suspected adverse reactions were collected in the first two years after bupropion's approval by the MHRA as part of the Yellow Card Scheme, which monitored side effects. The Medicines and Healthcare products Regulatory Agency (MHRA is the UK government agency which is responsible for ensuring that Medicines and Medical devices This article is about Human Medicines For Veterinary Medicines see the Suspected Adverse Reaction Surveillance Scheme. Approximately 540,000 people were treated with bupropion for smoking cessation during that period. The MHRA received 60 reports of "suspected [emphasis MHRA's] adverse reactions to Zyban which had a fatal outcome". The agency concluded that "in the majority of cases the individual’s underlying condition may provide an alternative explanation. "^[66] This is consistent with a large, 9,300-patient safety study that showed that the mortality of smokers taking bupropion is not higher than the natural mortality of smokers of the same age. ^[67]

Other isolated adverse affects have been reported. Three cases of liver toxicity have been described in the literature,^[68] a very low incidence given the widespread use of the drug. A single case of clitoral priapism (clitorism) has been reported in the literature. Priapism (πριαπισμός is a potentially harmful and painful medical condition in which the erect Penis does not return to its flaccid state despite Clitorism (/klɪt'ərɪzm/ from the Latin " Clitorismus " in turn from the Greek kleitoris + ismos, is a continued painful ^[69]

Overdose

Overdose of bupropion results in significant clinical effects in over one-third of cases. The term drug overdose (or simply overdose or OD) describes the Ingestion or application of a Drug or other substance in quantities ^[70] The most common symptoms include sinus tachycardia, hypertension, drowsiness, lethargy, agitation, nausea and vomiting, and in particular delirium and seizures. Sinus Tachycardia (also colloquially known as sinus tach or sinus tachy) is a rhythm with elevated rate of impulses originating from the Sinoatrial Hypertension, also referred to as high blood pressure, HTN or HPN, is a medical condition in which the Blood pressure is chronically elevated Delirium is an acute and relatively sudden (developing over hours to days decline in attention-focus perception and Cognition. An epileptic seizure is caused by excessive and/or hypersynchronous electrical Neuronal activity and is usually self-limiting ^[70][71][72] Less commonly additional symptoms include auditory and visual hallucinations,^[73] coma,^[72] and ECG changes such as conduction disturbance or arrhythmia. A hallucination, in the broadest sense is a Perception in the absence of a stimulus. In Medicine, a coma (from the Greek koma, meaning deep sleep is a profound state of Unconsciousness. Dysrhythmia redirects here For the American band see Dysrhythmia (band. ^[74][75][76]

In the majority of childhood exploratory ingestions involving one or two tablets, children will remain asymptomatic. ^[77][78] In teenagers and adults seizures are more commonly observed with the seizure rate increasing tenfold with doses of 600 mg daily. ^[79] One overdose study suggested a dose-dependent relationship with seizures; patients ingesting more than 4. 5 g were likely to have a seizure and nearly all patients ingesting more than 9 g had a seizure. ^[70]

There is no specific antidote for bupropion; treatment is supportive, and focuses on maintaining airway patency and controlling seizures with high dose intravenous benzodiazepines or barbiturates if seizures are refractory to benzodiazepines. The airways are those parts of the Respiratory system through which air flows to get from the external environment to the Alveoli. The benzodiazepines (pronounced, often abbreviated to "benzos") are a class of Psychoactive drugs with varying Hypnotic Barbiturates are drugs that act as central nervous system Depressants and by virtue of this they produce a wide spectrum of effects from mild Sedation ^[71] Gastric decontamination may be of little benefit given the risk of seizures and aspiration^[71] but activated charcoal is recommended,^[70] additionally whole bowel irrigation should be undertaken in those ingesting sustained release formulations. Activated carbon, also called activated charcoal or activated coal, is a form of Carbon that has been processed to make it extremely porous and thus to Whole bowel irrigation ( WBI) is a medical process involving the rapid administration of large volumes of an osmotically balanced Polyethylene glycol solution ^[71] Toxic effects may be delayed in onset, with seizures developing as late as 32 hours,^[71] subsequently patients should undergo electroencephalographic monitoring for 48 hours. ^[53]

Bupropion overdose rarely results in death, although cases have been reported. ^[74][80][81] Fatalities are typically associated with large overdosage and related to metabolic acidosis and hypoxia as complications of status epilepticus with associated cardiorespiratory arrest. In Medicine, metabolic acidosis is a process which if unchecked leads to acidemia (i Chronic Hypoxia is a pathological condition in which the body as a whole ( generalized hypoxia) or region of the body ( tissue hypoxia) is deprived of adequate Status epilepticus (SE refers to a life-threatening condition in which the Brain is in a state of persistent Seizure. A cardiac arrest, also known as cardiorespiratory arrest, cardiopulmonary arrest or circulatory arrest, is the abrupt cessation of normal circulation of ^[82] There is one published case report of successful treatment of refractory cardiac arrest in overdose of bupropion and lamotrigine using lipid rescue. Lamotrigine (marketed as Lamictal (ləˈmɪktəl by GlaxoSmithKline, called Lamictin in South Africa, he למוג'ין ( Lamogine Lipid Rescue is a term that has been coined to describe the use of intravenous lipid emulsion to treat severe Local anaesthetic toxicity ^[83]

Mechanism of action

Bupropion is a dopamine and norepinephrine reuptake inhibitor. Dopamine Reuptake Inhibitors ( DARI) Dopamine Uptake Inhibitors, Dopamine Transporter Inhibitors are compounds that inhibit the Reuptake of extracellular Norepinephrine reuptake inhibitors ( NRIs) also known as noradrenaline reuptake inhibitors ( NARIs) are compounds that elevate the extracellular level of ^[84] It is about twice as potent an inhibitor of dopamine reuptake than of norepinephrine reuptake. As bupropion is rapidly converted in the body into several metabolites with differing activity, its action cannot be understood without reference to its metabolism. The occupancy of dopamine transporter (DAT) by bupropion and its metabolites in the human brain as measured by positron emission tomography was 6–22% in an independent study^[85] and 12–35% according to GlaxoSmithKline researchers. The Dopamine transporter (also dopamine active transporter DAT SLC6A3 is a membrane-spanning protein that binds the Neurotransmitter Dopamine Positron emission tomography ( PET) is a Nuclear medicine imaging technique which produces a three-dimensional image or map of functional processes in the ^[86] Based on analogy with serotonin reuptake inhibitors, higher than 50% inhibition of DAT would be needed for the dopamine reuptake mechanism to be a major mechanism of the drug's action. Selective serotonin reuptake inhibitors ( SSRIs) are a class of Antidepressants used in the treatment of depression, Anxiety disorders Bupropion does not inhibit monoamine oxidase or serotonin reuptake. Serotonin (ˌsɛrəˈtoʊnən ( 5-hydroxytryptamine, or 5-HT) is a Monoamine Neurotransmitter synthesized in serotonergic Neurons However, it has been shown to indirectly enhance the firing of serotonergic neurons, via activation of downstream norepinephrine flow. Bupropion has also been shown to act as a noncompetitive α3β4 nicotinic antagonist. Structure Nicotinic receptors with a molecular mass of 290 kDa, are made up of five subunits arranged symmetrically around the central pore. A nicotinic antagonist is a type of Anticholinergic which inhibits the action at Nicotinic acetylcholine receptors These compounds are mainly used for peripheral muscle ^[87] The degree of inhibition of α3β4 receptors correlates well with the decrease in self-administration of morphine and methamphetamine in rats,^[88] and may be relevant to the effect of bupropion on nicotine addiction. The drug is supplied as a racemic mixture, and no studies have been published on the activities of the individual enantiomers. In Chemistry, a racemic mixture, or racemate, is one that has equal amounts of left- and right-handed enantiomers of a chiral ^[89]

Pharmacokinetics

Bupropion is metabolized in the liver. The liver is a vital organ in the human body and is present in Vertebrates and some other animals It has several active metabolites: R,R-hydroxybupropion, S,S-hydroxybupropion, threo-hydrobupropion and erythro-hydrobupropion, which are further metabolized to inactive metabolites and eliminated through excretion into the urine. Metabolomics is the "systematic study of the unique chemical fingerprints that specific cellular processes leave behind" - specifically the study of their small-molecule metabolite Pharmacological data on bupropion and its metabolites are presented in Table 1. Bupropion is known to weakly inhibit the α₁ adrenaline receptor, with a 14% potency of its dopamine uptake inhibition, and the H₁ receptor, with a 9% potency. The adrenergic receptors (or adrenoceptors) are a class of G protein-coupled receptors that are targets of the Catecholamines Adrenergic receptors The H1 receptor is a Histamine receptor, and thus an important target for clinically important drugs and is likely one of the most important receptors for modulating ^[90]

The biological activity of bupropion can be attributed to a significant degree to its active metabolites, in particular to S,S-hydroxybupropion. GlaxoSmithKline developed this metabolite as a separate drug called radafaxine,^[91] but discontinued development in 2006 due to "an unfavourable risk/benefit assessment". Radafaxine is Drug candidate designated 353162 by GlaxoSmithKline, investigated for treatment of Restless leg syndrome and as an NDRI antidepressant ^[92]

Bupropion is metabolized to hydroxybupropion by CYP2B6, an isoenzyme of the cytochrome P450 system. CYP2B6 is a member of the Cytochrome P450 group of enzymes Along with CYP2A6, it is involved with metabolizing Nicotine, along with many other substances Isozymes (also known as isoenzymes) are Enzymes that differ in amino acid sequence but catalyze the same chemical reaction Cytochrome P450 (abbreviated CYP, P450, infrequently CYP450) is a very large and diverse superfamily of Hemoproteins found in all Domains Alcohol causes an increase of CYP2B6 in the liver, and persons with a history of alcohol use metabolize bupropion faster. The mechanism of formation of erythro-hydrobupropion and threo-hydrobupropion has not been studied but is probably mediated by one of the carbonyl reductase enzymes. The metabolism of bupropion is highly variable: the effective doses of bupropion received by persons who ingest the same amount of the drug may differ by as much as 5. 5 times (and the half-life from 3 to 16 hours), and of hydroxybupropion by as much as 7. 5 times (and the half-life from 12 to 38 hours). ^[93][94]Based on this, some researchers have advocated monitoring of the blood level of bupropion and hydroxybupropion. ^[95]

There are significant interspecies differences in the metabolism of bupropion, with guinea pigs' metabolism of the drug being closest to that of humans. The Guinea pig (also commonly called the cavy after its scientific name Cavia porcellus) is a species of Rodent belonging to the family Caviidae ^[96] Particular caution is needed when extrapolating the results of experiments on rats to humans since hydroxybupropion, the main metabolite of bupropion in humans, is absent in rats. ^[97]

There have been two reported cases of false-positive urine amphetamine tests in persons taking bupropion. Bupropion metabolites erythro-hydrobupropion and threo-hydrobupropion, which have a phenethylamine structure resembling amphetamine are likely to have been responsible for this reaction. Phenethylamine, or β -phenylethylamine or 2-phenylethylamine is an Alkaloid and Monoamine. More specific follow-up tests were negative. ^[98][99]

Table 1. Pharmacology of bupropion and its metabolites. ^{[100][101][102][90][103]}

Exposure (concentration over time; bupropion exposure = 100%) and half-life
	Bupropion	R,R- Hydroxy bupropion	S,S- Hydroxy bupropion	Threo- hydro bupropion	Erythro- hydro bupropion
Exposure	100%	800%	160%	310%	90%
Half-life	10 h (IR) 17 h (SR)	21 h	25 h	26 h	26 h
Inhibition potency (potency of DA uptake inhibition by bupropion = 100%)
DA uptake	100%	0% (rat)	70% (rat)	4% (rat)	No data
NE uptake	27%	0% (rat)	106% (rat)	16% (rat)	No data
Ser uptake	2%	0% (rat)	4%(rat)	3% (rat)	No data
α3β4 nicotinic	53%	15%	10%	7% (rat)	No data
α4β2 nicotinic	8%	3%	29%	No data	No data
α1* nicotinic	12%	13%	13%	No data	No data
DA = dopamine; NE = norepinephrine; Ser = serotonin. Dopamine is a Hormone and Neurotransmitter occurring in a wide variety of animals including both vertebrates and invertebrates Norepinephrine ( INN) (abbreviated norepi or NE) or noradrenaline ( BAN) (abbreviated NA or NAd) is a Serotonin (ˌsɛrəˈtoʊnən ( 5-hydroxytryptamine, or 5-HT) is a Monoamine Neurotransmitter synthesized in serotonergic Neurons

Interactions

Since bupropion is metabolized to hydroxybupropion by the CYP2B6 enzyme, drug interactions with CYP2B6 inhibitors are possible: this includes medications like paroxetine, sertraline, norfluoxetine (the active metabolite of fluoxetine), diazepam, clopidogrel, and orphenadrine. CYP2B6 is a member of the Cytochrome P450 group of enzymes Along with CYP2A6, it is involved with metabolizing Nicotine, along with many other substances Diazepam (daɪˈæzɨpæm first marketed as Valium by Hoffmann-La Roche, is a Benzodiazepine derivative Drug. Clopidogrel is a potent oral antiplatelet agent often used in the treatment of Coronary artery disease, Peripheral vascular disease, and Cerebrovascular Orphenadrine (sold under the Brand names Norflex Mephenamin Disipal Banflex Flexon Biorphen Brocasipal and others is an Anticholinergic Drug of The expected result is the increase of bupropion and decrease of hydroxybupropion blood concentration. The reverse effect (decrease of bupropion and increase of hydroxybupropion) can be expected with CYP2B6 inducers, such as carbamazepine, clotrimazole, rifampicin, ritonavir, St John's Wort and others. Enzyme inhibitors are Molecules that bind to Enzymes and decrease their activity. Carbamazepine ("CBZ" is an Anticonvulsant and mood stabilizing drug used primarily in the treatment of Epilepsy and Bipolar disorder Clotrimazole is an Antifungal medication commonly used in the treatment of fungal infections of both humans and animals such as vaginal yeast infections and Rifampicin ( INN) (rɪˈfæmpəsɪn or rifampin ( USAN) is a Bactericidal Antibiotic drug of the Rifamycin group Ritonavir, with trade name Norvir St John's wort (pronounced) used alone refers to the species Hypericum perforatum, also known as Tipton's Weed or Klamath weed, but with qualifiers is ^[104]

Hydroxybupropion (but not bupropion) is itself an inhibitor of CYP2D6, as well as a substrate of that enzyme. Cytochrome P450 2D6 (CYP2D6 a member of the Cytochrome P450 mixed-function oxidase system is one of the most important enzymes involved in the metabolism of Xenobiotics A significant increase in the concentration of some drugs metabolized by CYP2D6 (venlafaxine, desipramine and dextromethorphan, but not fluoxetine or paroxetine) has been observed when they are taken with bupropion. Desipramine is a Tricyclic antidepressant (TCA that inhibits the reuptake of Norepinephrine. Dextromethorphan ( DXM or DM) is an Antitussive (cough suppressant drug found in many over-the-counter cold and Cough medicines ^[104][105]

Bupropion lowers the seizure threshold; accordingly, extreme care should be taken when prescribing bupropion with other medications that also lower it, such as antipsychotics, theophylline, steroids, and some tricyclic antidepressants. Theophylline, also known as dimethylxanthine, is a Methylxanthine drug used in therapy for Respiratory diseases such as COPD or Asthma A steroid is a Terpenoid Lipid characterized by a Carbon skeleton with four fused rings generally arranged in a 6-6-6-5 fashion Tricyclic antidepressants (abbreviation TCAs) are a class of Antidepressant drugs first used in the 1950s ^[53] Its combination with nicotine replacement therapies can elevate blood pressure; since this combination is no more effective than either a nicotine patch or bupropion alone, it is not recommended. Nicotine replacement therapy (NRT is the use of various forms of Nicotine delivery methods intended to replace nicotine obtained from smoking or other

The prescribing information recommends minimizing the use of alcohol, since in rare cases bupropion reduces alcohol tolerance, and because the excessive use of alcohol may lower the seizure threshold. ^[53] A small study conducted by GlaxoSmithKline indicated that bupropion (100 mg) may counteract the subjective effects of small doses of alcohol (16–32 mL, slightly less than 1–2 standard US drinks). The volunteers reported feeling more sober and clear-headed and less sedated. Bupropion also reduced the detrimental effect of alcohol on auditory vigilance. The combination of bupropion (100 mg) and two drinks of alcohol increased heart rate by six beats per minute, a statistically significant increase. ^[106]

Availability and dose forms

Brand-name and generic bupropion tablets are available in three forms, each as the hydrochloride salt: immediate release (Wellbutrin), sustained release (Wellbutrin SR), and extended release (Wellbutrin XL or XR). A salt, in Chemistry, is defined as the product formed from the neutralisation reaction of Acids and bases. Sustained-release ( SR) extended-release ( ER, XR, or XL) time-release or timed-release, controlled-release "Sustained release" and "extended release" are generally interchangeable terms, but in this case Wellbutrin SR is intended for twice-daily dosing and Wellbutrin XL is intended for once-daily dosing. Not all generics have retained this naming scheme, and the United States Pharmacopeia requires all prolonged-release drug formulations (including generics for Wellbutrin SR) to be labeled "extended release", which has caused confusion and medication errors. The United States Pharmacopeia is an official public standards–setting authority for all prescription and over–the–counter medicines and other health care products manufactured ^[107][108] According to GlaxoSmithKline, a 150 mg Wellbutrin SR tablet can be split in two and retain its sustained-release characteristics. ^[109] An extended-release form of bupropion hydrobromide was approved by the FDA in April 2008. Hydrobromic Acid is formed by dissolving the diatomic molecule Hydrogen bromide in water It will be marketed under the trade name Aplenzin. ^[110]

On October 11, 2007, two providers of consumer information on nutritional products and supplements, ConsumerLab.com and The People’s Pharmacy, released the results of comparative tests of different brands of bupropion. Events 1138 - A massive earthquake struck Aleppo, Syria. 1531 - Huldrych Zwingli is killed ConsumerLabcom ( CL) is a provider of independent test results of health wellness and nutrition products ^[111] The People's Pharmacy received multiple reports of increased side effects and decreased efficacy of generic bupropion, which prompted it to ask ConsumerLab. com to test the products in question. The tests showed that "one of a few generic versions of Wellbutrin XL 300 mg, sold as Budeprion XL 300 mg, didn't perform the same as the brand-name pill in the lab. "^[112] The FDA investigated these complaints and concluded that the Budeprion XL is equivalent to Wellbutrin XL in regards to bioavailability of bupropion and its main active metabolite hydroxybupropion. The FDA also noted that the coincidental natural mood variation is the most likely explanation for the apparent worsening of depression after the switch from Wellbutrin XL to Budeprion XL. ^[113]

In France, marketing authorization was granted on August 3, 2001, also solely as a smoking cessation aid, and with a maximum daily dose of 300 mg;^[114] only sustained-release bupropion is available. Events 8 - Roman Empire General Tiberius defeats Dalmatians on the river Bathinus. Year 2001 ( MMI) was a Common year starting on Monday according to the Gregorian calendar. Bupropion was granted a licence for use in adults with major depression in the Netherlands in early 2007, with GlaxoSmithKline expecting subsequent approval in other European countries. ^[115]

Abuse liability

According to the US government classification of psychiatric medications, bupropion is "non-abusable"^[116] or has low abuse potential. ^[117] In animal studies, however, squirrel monkeys^[118] and rats^[119] maintained the intravenous self-administration of bupropion, which may indicate abuse potential. The squirrel monkeys are the New World monkeys of the genus Saimiri. Intravenous therapy or IV therapy is the giving of Liquid substances directly into a Vein. However, significant interspecies differences of bupropion metabolism, particularly between rats and humans, make such extrapolations questionable. ^[120]

Two studies on drug abusers indicated that the subjective effects of bupropion are markedly different from those of amphetamine. Amphetamine, and related drugs such as Methamphetamine are a group of drugs that act by increasing levels of Norepinephrine, Serotonin, and Dopamine ^[121][122] Healthy volunteers trained to discriminate amphetamine and placebo recognized bupropion (400 mg) as amphetamine 20% of the time, compared to 10% for placebo and 75% for methylphenidate (20 mg). They also reported feeling alert, vigorous, elated and energetic, reflecting the general stimulating properties of bupropion. In contrast to amphetamine and methylphenidate, there was no feeling of "liking the drug" and no desire to take it again. ^[123] A comparison of bupropion SR (150 mg) and caffeine (178 mg) indicated that caffeine may have higher abuse liability since it resulted in more reports of pleasant feelings and a "high" than bupropion. Caffeine is a bitter white crystalline Xanthine Alkaloid that acts as a Psychoactive Stimulant Drug and a mild Diuretic ^[124]

There have been only four reports of bupropion abuse in the literature. Three cases described teenagers crushing and insufflating (snorting) the drug, two of them resulting in seizures. Insufflation (Latin insufflatio "blowing on or into" is the practice of inhaling substances into a Body cavity. ^{[125][126][127]} An additional case was reported where a teenager ingested bupropion believing the drug to be a stimulant. ^[128] An article on medication abuse in prisons mentions bupropion as one of the psychotropic medications commonly abused by inmates. ^[129]

References

External links

• Wellbutrin official website
• List of international brand names for bupropion
• Bupropion at the Open Directory Project
• Wellbutrin Pharmacology, Pharmacokinetics, Studies, Metabolism - Bupropion - RxList Monographs
• NAMI Wellbutrin
• Bupropion article from mentalhealth.com
• A Review of the Neuropharmacology of Bupropion, a Dual Norepinephrine and Dopamine Reuptake InhibitorPDF (94. The Open Directory Project ( ODP) also known as dmoz (from directory 7 KiB)

A kibibyte (a contraction of ki lo bi nary byte) is a unit of Information or Computer storage, established by the International

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