Amfebutamone, also known as bupropion, inhibits CYP2D6 with an IC50 of 58 μM[1]. Atypical antidepressants like bupropion cause endoplasmic reticulum stress and cytotoxicity in SH-SY5Y cells that is dependent on caspase [3]. By triggering the endoplasmic reticulum stress response and JNK activation, bupropion activates caspase 3, which causes apoptosis in SH-SY5Y cells [3]. 1–100 µg/mL of bupropion decreases cell viability. The apoptotic pathway may be the cause of the bupropion-induced reduction in cell viability [3]. Within an hour, bupropion (100 μg/mL) enhances the expression of phosphorylated versions of JNK, p38 MAPK, EIF-2α, and GRP78 [3].

In mice, amfebutamone exhibits both convulsant and anticonvulsant properties. Bupropion causes dose-dependent clonic convulsions in mice, with a convulsant dosage 50 (or CD50) of 119.7 mg/kg, which is the level at which 50% of mice have convulsions [4]. In male albino mice weighing 22–30 g, bupropion (10, 15, 20, and 40 mg/kg, i.p.) dose-dependently decreased immobility time in comparison to vehicle controls (in seconds). Bupropion was observed to decrease the immobility phase in the forced swim test and tail suspension test, with ED50 values of 18.5 and 18 mg/kg ip, respectively. Bupropion (10, 20, and 40 mg/kg, intraperitoneally) raises the concentration of homovanillic acid, a metabolite of free dopamine, in the mouse brain in a dose-dependent manner [5].

Cell Viability Assay [3]
Cell Types: SH-SY5Y human catecholaminergic cells
Tested Concentrations: 0, 1, 10, 50 and 100 µg/mL
Incubation Duration: 24 hrs (hours)
Experimental Results: Cell viability diminished Dramatically in a concentration-dependent manner.

---

Western Blot Analysis [3]
Cell Types: SH-SY5Y human catecholaminergic cells
Tested Concentrations: 100 μg/mL
Incubation Duration: 1, 3, 8, 24 hrs (hours)
Experimental Results: Immunity to p-EIF-2α within 1 hour of bupropion treatment Reactivity increased Dramatically and persisted for 3 hrs (hours), indicating that bupropion rapidly stimulates PERK. The expression of GRP78 was slightly but Dramatically increased and JNK was Dramatically activated. Early activation of ER stress pathways by bupropion returned to basal levels 8 hrs (hours) after treatment.

Animal/Disease Models: Male Swiss mouse, weight 20-25 grams [4]
Doses: 100-160 mg/kg
Route of Administration: IP
Experimental Results:Caused clonic convulsions, CD50 and CD97 were 119.7 (104.1-137.6) and 156.7 respectively mg/kg. When administered at the full convulsive dose of 160 mg/kg, the median latency was 6.00 minutes (3.50-8.15). Catalonic convulsions were only observed occasionally (1 in 8 mice) in groups receiving doses of 140 or 160 mg/kg.

Absorption, Distribution and Excretion
Bupropion hydrochloride is currently available in three different, but bioequivalent, formulations: immediate-release (IR), sustained-release (SR), and controlled-release (XL). Immediate-Release Formulations After oral administration of bupropion hydrochloride tablets in humans, peak plasma bupropion concentrations are typically reached within 2 hours. The immediate-release formulation has a short duration of action and is therefore usually taken three times daily. Sustained-Release Formulations After oral administration of bupropion hydrochloride sustained-release tablets (SR), peak plasma bupropion concentrations (Cmax) are typically reached within 3 hours. The sustained-release formulation provides sustained drug release for up to 12 hours and is therefore usually taken twice daily. Sustained-Release Formulations In healthy volunteers, the median time to peak plasma bupropion concentration after a single oral dose of bupropion hydrochloride sustained-release tablets (XL) is approximately 5 hours. The presence of food does not affect the peak concentration or area under the curve (AUC) of bupropion. The XL formulation provides 24-hour sustained drug release and is therefore usually taken once daily. In a chronic dosing trial comparing bupropion hydrochloride extended-release tablets (SR) 150 mg twice daily with bupropion immediate-release tablets 100 mg three times daily, the steady-state Cmax of bupropion after administration of SR was approximately 85% of the Cmax achieved after administration of the immediate-release tablets. The bupropion exposure (AUC) of the two formulations was comparable. Bioequivalence was demonstrated for both Cmax and AUC for all three major active metabolites: hydroxybupropion, threobupropion, and erythrobupropion. Therefore, at steady state, bupropion hydrochloride extended-release tablets (SR) twice daily are substantially bioequivalent to the immediate-release tablets three times daily for bupropion and its three important metabolites. Furthermore, in a study comparing a 14-day dosing regimen of 300 mg bupropion hydrochloride extended-release tablets (XL) once daily with a 100 mg bupropion immediate-release formulation three times daily, peak plasma concentrations and areas under the curve (AUC) of bupropion and its three metabolites (hydroxybupropion, threobupropion, and erythrobupropion) were confirmed to be equivalent. Additionally, a study comparing 300 mg bupropion hydrochloride extended-release tablets (XL) once daily with a 150 mg bupropion extended-release formulation twice daily for 14 days showed that the two formulations were equivalent in terms of peak plasma concentrations and AUC of bupropion and its three metabolites. Bupropion hydrochloride extended-release tablets (SR) can be taken with or without food. In three trials, when bupropion hydrochloride extended-release tablets (SR) were administered to healthy volunteers with food, the Cmax and AUC of bupropion increased by 11% to 35% and 16% to 19%, respectively. The effect of food was considered clinically insignificant. Following a single dose of bupropion hydrochloride extended-release tablets (SR) in humans, the peak plasma concentration (Cmax) of the bupropion metabolite hydroxybupropion occurred approximately 6 hours after administration, approximately 10 times the steady-state peak plasma concentration of the parent drug. The elimination half-life of hydroxybupropion was approximately 20 (±5) hours, and its steady-state AUC was approximately 17 times that of bupropion. The peak times of the erythrohydrobupropion and threohydrobupropion metabolites were similar to those of the hydroxybupropion metabolite. However, their elimination half-lives were longer, at 33 (±10) hours and 37 (±13) hours, respectively, and their steady-state AUCs were 1.5 times and 7 times that of bupropion, respectively. Bupropion is extensively metabolized in the human body. Oxidation of the bupropion side chain produces a glycine conjugate of m-chlorobenzoic acid, which is subsequently excreted as the main urinary metabolite. Following oral administration of 200 mg of 14C-bupropion in humans, 87% and 10% of the radioactive dose are recovered in urine and feces, respectively. However, only 0.5% of the oral bupropion dose is excreted unchanged, a result consistent with the extensive metabolism of bupropion. In healthy individuals, after oral administration of regular tablets or extended-release film-coated tablets (Wellbutrin SR, Zyban), peak plasma bupropion concentrations are typically reached within 2 to 3 hours. Following a single oral dose of 100–250 mg and chronic dosing up to 450 mg daily, plasma bupropion concentrations are dose-proportional. Steady-state plasma concentrations of bupropion hydrochloride are reached within 8 days. Long-term administration of bupropion hydrochloride in either immediate-release or extended-release film-coated tablets at doses of 100 mg three times daily or twice daily resulted in steady-state peak plasma concentrations of approximately 85% that of the immediate-release tablets. The area under the plasma concentration-time curve (AUC) was comparable for both formulations, indicating basic bioequivalence at steady state. Long-term administration of bupropion hydrochloride at daily doses of 300–450 mg exhibited linear pharmacokinetic characteristics. Following oral administration, bupropion hydrochloride is well absorbed from the gastrointestinal tract. Since there is currently no intravenous formulation, the oral bioavailability of bupropion hydrochloride in humans has not been elucidated. However, the relative proportion of the oral dose entering systemic circulation unchanged is likely small. In animals, the oral bioavailability of bupropion ranges from 5% to 20%. Food did not appear to significantly affect the peak plasma concentration or AUC of bupropion extended-release tablets; however, food has been reported to increase these parameters by 11% and 17%, respectively. Approximately 87% and 10% of the orally administered radiolabeled bupropion dose are excreted in urine and feces, respectively. Unmetabolized drug accounts for 0.5% of the excreted dose. Plasma concentrations of bupropion exhibit a biphasic decline. Six hours after a single oral administration, plasma bupropion concentrations decrease to approximately 30% of peak concentration. For more complete data on the absorption, distribution, and excretion of bupropion (9 types in total), please visit the HSDB record page. Metabolism/Metabolites Bupropion is extensively metabolized in the human body. Three active metabolites exist: hydroxybupropion, formed by the hydroxylation of bupropion tert-butyl; and amino alcohol isomers, threo-hydrobupropion and erythro-hydrobupropion, formed by carbonyl reduction. In vitro studies have shown that CYP2B6 is the major isoenzyme for the formation of hydroxybupropion, while cytochrome P450 enzymes do not participate in the formation of threo-hydrobupropion. Hydroxybupropion has the same affinity for norepinephrine transporter (NET) as bupropion, but its antidepressant activity is only about 50% that of bupropion, despite its concentration being about 10 times higher than the parent drug. Bupropion's side chain is oxidized to a glycine conjugate of m-chlorobenzoic acid, which is subsequently excreted as the main urinary metabolite. The potency and toxicity of these metabolites relative to bupropion are not fully understood. However, antidepressant screening studies in mice showed that hydroxybupropion is only half as potent as bupropion, while threo-hydrobupropion and erythro-hydrobupropion are 5 times less potent than bupropion. This may have clinical significance, as the plasma concentrations of these metabolites are comparable to or higher than those of bupropion. Following long-term daily administration of 300–450 mg bupropion and its metabolites, the pharmacokinetics of bupropion and its metabolites are linear. Bupropion appears to be extensively metabolized, likely primarily in the liver. Three active metabolites have been identified, formed via carbonyl reduction and/or hydroxylation. The identified basic metabolites include the erythroamino and threoamino alcohols of bupropion, and a morpholinol metabolite. The amino alcohol isomers threohydrobupropion and erythrohydrobupropion are generated by carbonyl reduction of bupropion, while the morpholinol metabolite hydroxybupropion is generated by tert-butyl hydroxylation of bupropion. Bupropion metabolites exhibit linear pharmacokinetic characteristics at long-term daily doses of 300–450 mg. Except for fluvoxamine and nefazodone, all marketed antidepressants are metabolized by and/or inhibit this isoenzyme, cytochrome P450 2D6 (CYP2D6). To date, no studies on this aspect of bupropion have been reported. We report that in 12 patients, the plasma concentration/dose ratio of bupropion and its metabolites erythrobupropion and threobupropion was not related to the metabolic status of desbroquine, including 3 patients with impaired CYP2D6 metabolism. However, the plasma concentration/dose ratio of the metabolite hydroxybupropion was significantly elevated in patients with impaired CYP2D6 metabolism. In 3 patients who underwent a second phenotypic test during bupropion treatment, the desbroquine metabolism ratio was not elevated. Therefore, it is inferred that bupropion is neither metabolized by CYP2D6 nor inhibits CYP2D6. However, the potential accumulation of hydroxybupropion after CYP2D6 inhibition may lead to toxicity and reduce the efficacy of bupropion. Bupropion hydrochloride is a novel monocyclic antidepressant. In the human body, bupropion is primarily metabolized to three metabolites: morpholinol metabolite, erythroaminool metabolite, and threoaminool metabolite. This study monitored the metabolism of bupropion in 8 healthy volunteers and 8 age-(44.5±8.4 years) and weight-matched patients with alcoholic liver disease (77.4±6.7 kg) after a single oral dose of 200 mg. The latter group is noteworthy because the incidence of depression is higher in alcoholic patients than in the general population, and the liver is the main metabolic pathway for cyclic antidepressants. In patients with alcoholic liver disease, the mean elimination half-life of morpholinol metabolites was significantly prolonged (32.2 ± 13.5 h vs. 21.1 ± 4.9 h, p < 0.05), while the differences for bupropion (17.3 ± 8.6 h in healthy subjects and 16.5 ± 10.4 h in patients with alcoholic liver disease), erythroaminol (26.1 ± 13.3 h in healthy subjects and 29.8 ± 6.9 h in patients with alcoholic liver disease), and threoaminol (25.5 ± 8.6 h in healthy subjects and 23.4 ± 10.7 h in patients with alcoholic liver disease) were small. The mean area under the plasma concentration-time curve for bupropion and its metabolites was increased in patients with alcoholic liver disease; however, the mean differences between these small sample groups were not significant. These results may be due to increased variability in the pharmacokinetics of bupropion in these subjects. For patients with chronic alcoholism who may be taking antidepressants and drinking alcohol concurrently, the lack of sedation in bupropion may be an advantage, thus making it a potential treatment for depression. We investigated the steady-state pharmacokinetics of the monocyclic aminoketone antidepressant bupropion hydrochloride in patients with depression. At steady state, the concentrations of the metabolites hydroxybupropion (HB), threobupropion, and erythrobupropion in plasma and cerebrospinal fluid were all higher than those of the parent compound. Plasma concentrations of each metabolite correlated with cerebrospinal fluid concentrations. Higher plasma metabolite concentrations were associated with adverse clinical outcomes. This correlation was most significant with HB; plasma HB levels were above 1250 ng/mL in all 5 non-responders, while they were below 1200 ng/mL in all 7 responders. Plasma HB levels correlated with post-treatment plasma homovanillic acid levels. High levels of bupropion metabolites may be associated with dopaminergic system toxicity leading to adverse clinical outcomes. Furthermore, bupropion metabolites may exhibit a dose-response relationship. Future research should explore the clinical application value of plasma metabolite detection in improving the efficacy of bupropion treatment. For more complete data on the metabolism/metabolites of bupropion (9 metabolites in total), please visit the HSDB record page. Bupropion undergoes carbonyl reduction and/or tert-butyl hydroxylation. Elimination pathway: Bupropion is extensively metabolized in the human body. Oxidation of the bupropion side chain generates a glycine conjugate of m-chlorobenzoic acid, which is subsequently excreted as the main urinary metabolite. After oral administration of 200 mg, 87% and 10% of the radioactive dose of 14C-bupropion are recovered in urine and feces, respectively. However, only 0.5% of oral bupropion is excreted unchanged, a result consistent with the extensive metabolism of bupropion.
Half-life: 24 hours
Biological half-life
24 hours
After a single dose, the average terminal half-life of bupropion is approximately 14 hours (range: 8–24 hours); after multiple doses, the average terminal half-life of bupropion has been reported to be 21 hours (range: 8–39 hours). In a small number of elderly patients with severe depressive episodes, the average terminal half-life of bupropion after a single oral dose is approximately 34 hours.

Toxicity Summary
Identification and Uses: Bupropion is a pale yellow oil formulation made into sustained-release oral tablets. Bupropion is a dopamine reuptake inhibitor used as a second-generation antidepressant. Human Exposure and Toxicity: Bupropion is a commonly used antidepressant and is also frequently used as an aid to smoking cessation. It affects dopamine and norepinephrine and may lower the seizure threshold, especially in cases of overdose. Several cases of recreational use of bupropion via nasal inhalation have been reported in the literature. One of the most serious potential adverse effects of bupropion is a lowering of the seizure threshold. However, although this effect can be severe, seizures remain a relatively rare adverse effect of bupropion treatment. Overdoses of 30 grams or more of bupropion hydrochloride have been reported. Serious consequences of bupropion overdose include seizures, hallucinations, loss of consciousness, sinus tachycardia, and ECG changes such as conduction disturbances or arrhythmias in approximately one-third of patients. In addition, drowsiness, lethargy, tremors, anxiety, confusion, dizziness, paresthesia, visual hallucinations, blurred vision, nausea, and vomiting may occur. Bupropion overdose (primarily as part of multiple drug overdoses) has been reported to cause fever, muscle stiffness, rhabdomyolysis, hypotension, coma, lethargy, and respiratory failure. Most people who overdose on bupropion alone recover without sequelae. However, there are also reports of death in rare cases of large doses of bupropion alone, preceded by multiple uncontrollable seizures, bradycardia, heart failure, and cardiac arrest. Cardiotoxicity appears to be primarily caused by bupropion rather than its active metabolite, hydroxybupropion. Accidental ingestion of bupropion by young children usually results in only mild toxicity. In two deaths attributed to bupropion, the estimated doses were both less than 10 grams. Animal studies: In lifetime carcinogenicity studies in rats and mice, administration of bupropion hydrochloride at daily doses of 100-300 or 150 mg/kg, respectively, resulted in an increase in nodular proliferative lesions in the liver of rats, but not in mice. The relationship between these lesions and the development of liver tumors is unclear. No increase in malignant tumors of the liver or other organs was observed in either rats or mice. In a fertility study in rats, oral administration of bupropion hydrochloride at doses up to 300 mg/kg daily did not reveal evidence of impaired fertility. Oral administration of bupropion at doses up to 300 mg/kg daily in rats before mating and throughout pregnancy and lactation did not show significant adverse effects on offspring development. In developmental studies in rats and rabbits, no definite teratogenic activity was found in either animal group, but a slight increase in the incidence of fetal malformations and skeletal variations was observed in rabbits. Bupropion can cause behavioral changes in rats and mice. Bupropion exhibited mutagenic activity in the Salmonella microbial mutagen (Ames) assay system; in two of the five strains, the mutation rate was 2-3 times higher than that of the control group. In one of three in vivo cytogenetic studies of rat bone marrow, increased chromosomal aberrations were observed. Bupropion selectively inhibits the reuptake of dopamine, norepinephrine, and serotonin by neurons; its effect on the dopaminergic system is more significant compared to imipramine or amitriptyline; however, compared to tricyclic antidepressants, bupropion has a weaker blocking effect on the reuptake of norepinephrine and serotonin by neuronal membranes. Increased norepinephrine may alleviate nicotine withdrawal symptoms, while increased dopamine in neuronal sites may reduce nicotine cravings and the urge to smoke. Bupropion has moderate anticholinergic effects.

---

Drug Interactions
Uncommon adverse neuropsychiatric events or decreased alcohol tolerance have been reported in patients who drink alcohol while taking bupropion. Because of concerns that excessive drinking or abrupt abstinence may be associated with an increased risk of seizures during bupropion treatment, patients taking this medication should be advised to minimize or avoid alcohol consumption as much as possible.
Concomitant use of bupropion and carbamazepine resulted in a decrease of 87% and 90% in peak plasma concentration and 24-hour area under the plasma concentration-time curve (AUC) of bupropion, respectively; and an increase of 71% and 50% in peak plasma concentration and 24-hour AUC of the metabolite hydroxybupropion, respectively.138In contrast, concomitant use of bupropion with sodium valproate resulted in only a 94% increase in the 24-hour AUC of hydroxybupropion. ¹³⁸A small number of Parkinson's syndrome patients receiving amantadine or levodopa treatment have a higher incidence of adverse reactions (such as nausea and vomiting, agitation and restlessness, postural tremor) when using bupropion concurrently. Caution should be exercised when initiating bupropion treatment in patients currently receiving levodopa or amantadine, including starting with a low initial dose and gradually increasing the dose in small increments.
Animal studies suggest a potential danger associated with the concomitant use of bupropion with monoamine oxidase (MAO) inhibitors. In animal studies, phenelzine enhanced the acute toxicity of bupropion, manifested as increased mortality and shortened time to death. The manufacturer states that concomitant use of bupropion with monoamine oxidase inhibitors (MAO inhibitors) is contraindicated, and that MAO inhibitors should be discontinued at least 2 weeks before initiating bupropion treatment.
For more complete data on drug interactions with bupropion (out of 20 items), please visit the HSDB record page.

---

Non-human toxicity values
Mouse intraperitoneal LD50: 230 mg/kg
Mouse oral LD50: 575 mg/kg
Rat intraperitoneal LD50: 210 mg/kg
Rat oral LD50: 600 mg/kg

[1]. C Lindsay DeVane. Antidepressant-drug interactions are potentially but rarely clinically significant. Neuropsychopharmacology. 2006 Aug;31(8):1594-604; discussion 1614-5.

[2]. Bupropion, methylphenidate, and 3,4-methylenedioxypyrovalerone antagonize methamphetamine-induced efflux of dopamine according to their potencies as dopamine uptake inhibitors: implications for the treatment of methamphetamine depe.

[3]. Bupropion, an atypical antidepressant, induces endoplasmic reticulum stress and caspase-dependent cytotoxicity in SH-SY5Y cells. Toxicology. 2011 Jul 11;285(1-2):1-7.

[4]. Convulsant and anticonvulsant effects of bupropion in mice. Eur J Pharmacol. 2004 Sep 19;499(1-2):117-20.

[5]. Moreira, R., The efficacy and tolerability of bupropion in the treatment of major depressive disorder. Clin Drug Investig, 2011. 31 Suppl 1: p. 5-17.

Therapeutic Uses

Second-generation antidepressant; dopamine reuptake inhibitor
Zyban is indicated as an adjunct to smoking cessation therapy. /US product label includes/
Wellbutrin XL is indicated for the treatment of major depressive disorder. /US product label includes/
Wellbutrin XL is indicated for the prevention of seasonal major depressive episodes in patients diagnosed with seasonal affective disorder.
For more complete data on the therapeutic uses of bupropion (9 of these), please visit the HSDB record page.

---

Drug Warnings
/Black Box Warning/ Warning: Neuropsychiatric reactions have occurred in patients taking bupropion to quit smoking. Serious neuropsychiatric reactions have been reported in patients taking Zyban to quit smoking. Most of these reactions occurred during bupropion treatment, but some occurred after discontinuation. In many cases, a causal relationship between these reactions and bupropion treatment cannot be established, as depressed mood can be a symptom of nicotine withdrawal. However, some such symptoms have also occurred in patients taking bupropion (Zyban) but continuing to smoke. The risks and benefits of bupropion should be weighed. Studies have shown that bupropion can improve smoking cessation success rates compared to placebo, up to 6 months. The health benefits of quitting smoking are immediate and significant. /Black Box Warning/ Warning: Suicidal Tendencies and Antidepressants. Although bupropion (Zyban) is not used to treat depression, it contains the same active ingredient as the antidepressants Wellbutrin SR and Wellbutrin XL. Short-term trials have shown that antidepressants increase the risk of suicidal ideation and behavior in children, adolescents, and young adults. These trials did not show an increased risk of suicidal ideation and behavior in subjects aged 24 and older; and a reduced risk in subjects aged 65 and older. Patients of all ages starting antidepressant treatment should be closely monitored for worsening conditions and the occurrence of suicidal ideation and behavior. Family members and caregivers should be informed of the need for close monitoring and communication with the prescribing physician. /Warning (Black Box)/ Warning: Suicidal Tendency and Antidepressants. For the treatment of mental illness: In short-term studies of major depressive disorder (MDD) and other mental illnesses, antidepressants have increased the risk of suicidal ideation and behavior (suicidal tendencies) in children, adolescents, and young adults compared to placebo. Anyone considering the use of bupropion extended-release tablets (Wellbutrin XL) or any other antidepressant in children, adolescents, or young adults must weigh the risks against clinical need. Short-term studies have shown that antidepressant use in adults 24 years of age and older did not increase the risk of suicide compared to placebo; however, it did reduce the risk of suicide in adults 65 years of age and older compared to placebo. Depression and certain other mental illnesses are themselves associated with an increased risk of suicide. Patients of all ages starting antidepressant treatment should be appropriately monitored for worsening conditions, suicidal tendencies, or abnormal changes in behavior. Family members and caregivers should be informed of the need for close monitoring and communication with the prescribing physician. Bupropion extended-release tablets (Wellbutrin XL) are not approved for use in children. /Warning (Black Box)/ Warning: For smoking cessation treatment: Bupropion hydrochloride (Wellbutrin), bupropion hydrochloride extended-release tablets (Wellbutrin SR), and bupropion hydrochloride extended-release tablets (Wellbutrin XL) are not approved for smoking cessation treatment, but bupropion under the brand name Zyban is approved for this purpose. Serious neuropsychiatric events, including but not limited to depression, suicidal ideation, suicide attempts, and suicide deaths, have been reported in patients using bupropion to quit smoking. Some cases may be complicated by nicotine withdrawal symptoms. Depressed mood may be one of the symptoms of nicotine withdrawal. Smokers who have tried to quit without medication have reported depressive symptoms, with suicidal ideation in rare cases. However, these symptoms have also been reported in some patients who continued to smoke despite using bupropion. All patients receiving bupropion (Zyban) for smoking cessation should be monitored for neuropsychiatric symptoms, including behavioral changes, hostility, agitation, depressed mood, and suicide-related events such as suicidal ideation, suicidal behavior, and suicide attempts. Post-marketing experience has shown that some patients using bupropion (Zyban) for smoking cessation have reported the above symptoms, as well as exacerbations of pre-existing mental illness and suicide. Most reported symptoms occurred during bupropion treatment, but some occurred after discontinuation. These events occurred in both patients with and without a history of mental illness; some patients experienced exacerbations of their mental illness. Patients with severe mental illnesses (e.g., schizophrenia, bipolar disorder, and major depressive disorder) were not included in pre-marketing studies of bupropion (Zyban). Patients and their caregivers should be informed that if a patient using bupropion for smoking cessation experiences agitation, hostility, depressed mood, or abnormal changes in thinking or behavior (unlike the patient's previous behavior), or experiences suicidal ideation or behavior, they should immediately discontinue bupropion and contact a healthcare provider. Post-marketing reports indicate that many patients experienced symptom relief after discontinuing bupropion, but some cases showed persistent symptoms; therefore, continued monitoring and supportive care should be provided until symptoms subside. The risks and benefits of using bupropion for smoking cessation should be weighed. Studies have shown that bupropion can improve smoking cessation success rates by up to six months compared to placebo. The health benefits of quitting smoking are immediate and significant. For more complete data on bupropion (41 total warnings), please visit the HSDB records page.

---

Pharmacodynamics
Bupropion is chemically unrelated to tricyclic, tetracyclic, selective serotonin reuptake inhibitors, or other known antidepressants. Compared to classic tricyclic antidepressants, bupropion has a relatively weaker inhibitory effect on neuronal uptake of norepinephrine and dopamine. Furthermore, bupropion does not inhibit monoamine oxidase. Studies have found that bupropion has almost no activity against serotonin transporter (SERT) (IC50 > 10000 nM), but both bupropion and its major metabolite, hydroxybupropion, can block the function of the cationic selective serotonin type 3A receptor (5-HT3AR). Bupropion produces dose-dependent central nervous system (CNS) excitatory effects in animals, manifested as enhanced motor activity, increased response rates in various programmed operant behavioral tasks, and the induction of mild stereotyped behaviors at high doses. Due to these excitatory effects and selective activity against dopamine and norepinephrine receptors, bupropion is considered to have abuse potential. Bupropion's structure is similar to the controlled substance [DB01560] and has been shown to have mild amphetamine-like activity, especially upon inhalation or injection. Bupropion is known to lower the seizure threshold; therefore, any pre-existing history of epilepsy constitutes a contraindication to its use. This risk is exacerbated when bupropion is used in combination with other drugs or substances that lower the seizure threshold (such as cocaine), or when used in clinical situations that increase the risk of seizures (such as sudden withdrawal from alcohol or benzodiazepines). Because norepinephrine has been shown to have anticonvulsant effects, bupropion's inhibition of the norepinephrine transporter (NET) is thought to be related to its proconvulsant activity. Bupropion has been shown to raise blood pressure and may worsen uncontrolled or pre-existing hypertension; however, clinical trials of bupropion in smokers with cardiovascular disease have not found an increased incidence of cardiovascular events (including stroke or heart attack). In clinical trials, the average increase in systolic blood pressure caused by bupropion use was 1.3 mmHg.

C13H18NOCL

239.74112

239.108

34911-55-2

Bupropion hydrochloride;31677-93-7;Bupropion hydrobromide;905818-69-1

444

Pale yellow oil

1.066g/cm3

334.8ºC at 760mmHg

233-234°C

156.3ºC

3.69

1

2

4

16

247

0

CC(C(=O)C1=CC(=CC=C1)Cl)NC(C)(C)C

SNPPWIUOZRMYNY-UHFFFAOYSA-N

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

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

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

---

Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

View More

Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

---

Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

View More

Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

---

Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

---

 (Please use freshly prepared in vivo formulations for optimal results.)