Bupropion
|
|
| Systematic (IUPAC) name |
| (±)-2-(tert-Butylamino)-1-(3-chlorophenyl)propan-1-one |
| Clinical data |
| Trade names |
Wellbutrin, Zyban |
| AHFS/Drugs.com |
monograph |
| MedlinePlus |
a695033 |
| Licence data |
US FDA:link |
| Pregnancy cat. |
B2 (AU) C (US) |
| Legal status |
Prescription Only (S4) (AU) ℞-only (CA) POM (UK) ℞-only (US) |
| Dependence liability |
very low |
| Routes |
Oral |
| Pharmacokinetic data |
| Protein binding |
84% (bupropion), 77% (hydroxybupropion metabolite), 42% (threohydrobupropion metabolite)[1] |
| Metabolism |
Hepatic (mostly CYP2B6-mediated hydroxylation, but with some contributions from CYP1A2, CYP2A6, CYP2C9, CYP3A4, CYP2E1)[1][2][3] |
| Half-life |
11 hours (short-term dosing; parent compound)[4] 14-21 hours (chronic dosing; parent compound - depends on formulation),[1][3][5] 20 hours (hydroxybupropion), 33 hours (erythrohydrobupropion), 37 hours (threohydrobupropion)[1][3][5][6] |
| Excretion |
Renal (87%; 0.5% unchanged), Faecal (10%)[2][3][5] |
| Identifiers |
| CAS number |
34841-39-9 Y |
| ATC code |
N06AX12 |
| PubChem |
CID 444 |
| DrugBank |
DB01156 |
| ChemSpider |
431 Y |
| UNII |
01ZG3TPX31 Y |
| KEGG |
D07591 Y |
| ChEBI |
CHEBI:3219 Y |
| ChEMBL |
CHEMBL894 Y |
| Chemical data |
| Formula |
C13H18ClNO |
| Mol. mass |
239.74 g/mol |
SMILES
- O=C(C(C)NC(C)(C)C)C1=CC=CC(Cl)=C1
|
InChI
-
InChI=1S/C13H18ClNO/c1-9(15-13(2,3)4)12(16)10-6-5-7-11(14)8-10/h5-9,15H,1-4H3 Y
Key:SNPPWIUOZRMYNY-UHFFFAOYSA-N Y
|
| N (what is this?) (verify) |
Bupropion (// bew-PROH-pee-on;[7]) is a drug primarily used as an atypical antidepressant and smoking cessation aid. Marketed as Wellbutrin, Budeprion, Prexaton, Elontril, Aplenzin, or other trade names, it is one of the most frequently prescribed antidepressants in the United States. Marketed in lower-dose formulations as Zyban, Voxra, or other names, it is also widely used to reduce nicotine cravings by people who are trying to quit smoking. It is taken in the form of pills, and in the United States is available only by prescription.
Medically, bupropion serves as a non-tricyclic antidepressant fundamentally different from most commonly prescribed antidepressants such as selective serotonin reuptake inhibitors (SSRIs). It is an effective antidepressant on its own, but is also popular as an add-on medication in cases of incomplete response to first-line SSRI antidepressants. In contrast to many other antidepressants, it does not cause weight gain or sexual dysfunction. The most important side effect is an increase in risk for epileptic seizures, which caused the drug to be withdrawn from the market for some time and then caused the recommended dosage to be reduced. 300 mg a day (for average body weight) has been shown to maintain the same 0.1% unprovoked seizure rate of the general population.
Bupropion affects a number of neurotransmitter systems, and its mechanisms of action are only partly understood. A norepinephrine-dopamine reuptake inhibitor, the primary pharmacological action of the drug is as a mild dopamine reuptake inhibitor and also a much weaker norepinephrine reuptake inhibitor as well as a nicotinic acetylcholine receptor antagonist. Chemically, bupropion belongs to the class of aminoketones and is similar in structure to stimulants such as cathinone and amfepramone, and to phenethylamines in general.
Bupropion was patented in 1969 by Burroughs Wellcome, which later became part of what is now GlaxoSmithKline. It was originally called amfebutamone, before being renamed in 2000.[8] Its chemical name is 3-chloro-N-tert-butyl-β-ketoamphetamine. It is a substituted cathinone (β-ketoamphetamine), as well as a substituted amphetamine.
Contents
- 1 Medical uses
- 1.1 Depression
- 1.2 Smoking cessation
- 1.3 Seasonal Affective Disorder
- 1.4 Attention deficit hyperactivity disorder
- 1.5 Sexual dysfunction
- 1.6 Obesity
- 1.7 Other uses
- 2 Adverse effects
- 2.1 Psychiatric
- 2.2 Contraindications
- 2.3 Interactions
- 2.4 Overdose
- 3 Pharmacology
- 4 Pharmacokinetics
- 5 Synthesis
- 6 Regulatory history
- 7 Recreational use
- 8 References
- 9 External links
Medical uses[edit]
Depression[edit]
Bupropion is one of the most widely prescribed antidepressants, and the available evidence indicates that it is effective in clinical depression[9] — as effective as several other widely prescribed drugs, including fluoxetine (Prozac) and paroxetine (Paxil).[10] Although trends favouring greater efficacy of escitalopram (Lexapro), sertraline (Zoloft) and venlafaxine (Efexor, Effexor) than bupropion have been observed.[10] Mirtazapine (Avanza, Axit, Remeron), on the other hand is significantly more efficacious than bupropion.[10] It has several features that distinguish it from other antidepressants: for instance, unlike the majority of antidepressants, bupropion does not usually cause sexual dysfunction.[11] Bupropion treatment also is not associated with the somnolence or weight gain that may be produced by other antidepressants.[12]
The majority of depressed people suffer from insomnia, but there are some who instead experience constant sleepiness and fatigue. In this subgroup, bupropion has been found to be more effective than selective serotonin reuptake inhibitors (SSRIs) at alleviating the symptoms.[13] There appears to be a modest advantage for the SSRIs compared to bupropion in the treatment of anxious depression.[14]
According to surveys, the augmentation of a prescribed SSRI with bupropion is a common strategy among clinicians when the patient does not respond to the SSRI, even though this is not an officially approved indication for prescription.[15] The addition of bupropion to an SSRI (most commonly fluoxetine or sertraline) results in a significant improvement in the majority of patients who have an incomplete response to the first-line antidepressant.[15]
In some countries (including Australia, New Zealand and the UK) this is an off-label use.[16][17]
Smoking cessation[edit]
The next most common use is as an aid for smoking cessation, where it is marketed by GlaxoSmithKline under the trade name Zyban, or by other makers as a generic equivalent.
Numerous studies have provided evidence that bupropion substantially reduces the severity of nicotine cravings and withdrawal symptoms.[18] For example, in one large-scale study, 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. In the same study, 21% of the bupropion group reported mood swings, versus 32% of the placebo group.[19] A typical bupropion treatment course lasts for seven to twelve weeks, with the patient halting the use of tobacco about ten days into the course. Bupropion approximately doubles the chance of quitting smoking successfully after three months. One year after treatment, the odds of sustaining smoking cessation are still 1.5 times higher in the bupropion group than in the placebo group.[18]
The evidence is clear that bupropion is effective at reducing nicotine cravings. Whether it is more effective than other treatments is not as clear, due to a limited number of studies. The evidence that is available suggests that bupropion is comparable to nicotine replacement therapy, but somewhat less effective than varenicline (Chantix).[18]
In Australia and the UK smoking cessation is the only licensed indication of bupropion.[16][17]
Seasonal Affective Disorder[edit]
Bupropion was approved by the U.S. Food and Drug Administration (FDA), in 2006, for the prevention of seasonal affective disorder.[20] It was the first drug approved specifically for this condition.
Attention deficit hyperactivity disorder[edit]
There have been numerous reports of positive results for bupropion as a treatment for attention deficit hyperactivity disorder (ADHD), both in minors and adults.[21] However, in the largest to date double-blind study of children, 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.[21] 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."[22] Similarly, the Texas Department of State Health Services guideline recommends considering bupropion or a tricyclic antidepressant as a fourth-line treatment after trying two different stimulants and atomoxetine.[23]
Sexual dysfunction[edit]
Bupropion is one of few antidepressants that do not cause sexual dysfunction.[24] A range of studies demonstrate that bupropion not only produces fewer sexual side effects than other antidepressants, but can actually help to alleviate sexual dysfunction.[25] According to a survey of psychiatrists, it is the drug of choice for the treatment of SSRI-induced sexual dysfunction, although this is not an indication approved by the U.S. Food and Drug Administration. 36% of psychiatrists preferred switching patients with SSRI-induced sexual dysfunction to bupropion, and 43% favored the augmentation of the current medication with bupropion.[26] There have also been a few studies suggesting that bupropion can improve sexual function in women who are not depressed, if they have hypoactive sexual desire disorder.[27]
Obesity[edit]
A recent meta-analysis of anti-obesity medications pooled the results of three double-blind, placebo-controlled trials of bupropion. 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). It was not, however, significantly different from the weight loss produced by several other established medications, such as sibutramine, orlistat and amfepramone.[28]
Other uses[edit]
There has been controversy about whether it is useful to add an antidepressant such as bupropion to a mood stabilizer in patients with bipolar depression, but recent reviews have concluded that bupropion in this situation does no significant harm and may sometimes give significant benefit.[29][30]
Bupropion has shown no effectiveness in the treatment of cocaine dependence, but there is weak evidence that it may be useful in treating methamphetamine dependence.[31]
Based on studies indicating that bupropion lowers the level of the inflammatory mediator TNF-alpha, there have been suggestions that it might be useful in treating inflammatory bowel disease or other autoimmune conditions, but very little clinical evidence is available.[32]
Bupropion—like other antidepressants, with the exception of duloxetine (Cymbalta)[33]—is not effective in treating chronic low back pain.[34] It does, however, show some promise in the treatment of neuropathic pain.[35]
Adverse effects[edit]
Incidences of adverse effects[1][2][3][5][16][17]
- Very common (>10%) adverse effects include
- Insomnia (which can usually be avoided by avoiding dosing near to bedtime. It is usually transient)
- Headache
- Common (1-10%) adverse effects include
- Fever
- Asthenia
- Dizziness
- Agitation
- Anxiety
- Alopecia
- Tremor
- Concentration disturbance
- Depression
- Dry mouth
- Nausea
- Vomiting
- Constipation
- Abdominal pain
- Rash
- Pruritus (itchiness)
- Sweating
- Urticaria (indicative of a hypersensitivity reaction)
- Visual disturbance
- Taste disorders
- Uncommon (0.1-1%) adverse effects include
- Chest pain
- Flushing
- Tachycardia (high heart rate)
- Increased blood pressure
- Confusion
- Anorexia
- Tinnitus
- Rare (0.01-0.1%) adverse effects include
- Postural hypotension
- Vasodilation
- Syncope
- Hypotension
- Palpitations
- Hallucinations
- Irritability
- Hostility
- Seizures
- Depersonalization
- Parkinsonism
- Dystonia
- Ataxia
- Incoordination
- Twitching
- Abnormal dreams
- Memory impairment
- Paraesthesia
- Delusions
- Paranoid ideation
- Aggression
- Restlessness
- Blood glucose disturbances
- Arthralgia
- Myalgia
- Erythema multiforme
- Stevens Johnson syndrome
- Urinary retention
- Urinary frequency
- Elevated liver enzymes
- Jaundice
- Hepatitis
- Malaise
- Angioedema (which is indicative of a hypersensitivity reaction)
- Dyspnoea (also indicative of a hypersensitivity reaction)
- Bronchospasm (also indicative of a hypersensitivity reaction)
- Anaphylactic shock (also indicative of a hypersensitivity reaction)
- A condition similar to serum sickness
Epileptic seizures are the most important adverse effect of bupropion. A high incidence of seizures was responsible for the temporary withdrawal of the drug from the market between 1986 and 1989. The risk of seizure is strongly dose-dependent, but also dependent on the preparation. The sustained-release preparation is associated with a seizure incidence of 0.1% at daily dosages of less than 300 mg of bupropion and 0.4% at 300–400 mg.[36] The immediate release preparation is associated with a seizure incidence of 0.4% for dosages below 450 mg; the incidence climbs to 5% for dosages between 450–600 mg per day.[36] For comparison, the incidence of unprovoked seizure in the general population is 0.07 to 0.09%, and the risk of seizure for a variety of other antidepressants is generally between 0 and 0.6% at recommended dosage levels.[37] Given that clinical depression itself has been reported to increase the occurrence of seizures, it has been suggested that low to moderate doses of antidepressants may not actually increase seizure risk at all.[38] However, this same study found that bupropion and clomipramine were unique among antidepressants in that they were associated with increased incidence of seizures.[38]
The prescribing information notes that hypertension, sometimes severe, was observed in some patients, both with and without pre-existing hypertension. The frequency of this adverse effect was under 1% and not significantly higher than found with placebo.[39] A review of the available data carried out in 2008 indicated that bupropion is safe to use in patients with a variety of serious cardiac conditions.[40]
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 Medicines and Healthcare Products Regulatory Agency as part of the Yellow Card Scheme, which monitored side effects. 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."[41] 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.[42]
Psychiatric[edit]
Suicidal thought and behavior are rare in clinical trials, and the FDA requires all antidepressants, including bupropion, to carry a boxed warning stating that antidepressants may increase the risk of suicide in persons younger than 25. This warning is based on a statistical analysis conducted by the FDA which found a 2-fold increase in suicidal thought and behavior in children and adolescents, and 1.5-fold increase in the 18–24 age group.[43] For this analysis the FDA combined the results of 295 trials of 11 antidepressants in order to obtain statistically significant results. Considered in isolation, bupropion was not statistically different from placebo.[43]
Suicidal behavior is less of a concern when bupropion is prescribed for smoking cessation. According to a 2007 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 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."[44]
In 2009 the FDA issued a health advisory warning that the prescription of bupropion for smoking cessation has been associated with reports about unusual behavior changes, agitation and hostility. Some patients, according to the advisory, have become depressed or have had their depression worsen, have had thoughts about suicide or dying, or have attempted suicide.[45] This advisory was based on a review of anti-smoking products that identified 75 reports of "suicidal adverse events" for bupropion over ten years.[46]
Bupropion-induced psychosis may develop in select patient populations, or worsen a pre-existing psychotic syndrome.[47] Symptoms may include delusions, hallucinations, paranoia, and confusion. In most cases these symptoms can be reduced or eliminated by reducing the dose, ceasing treatment or adding antipsychotic medication.[39][47][48] However, adding a benzodiazepine to treat psychosis, instead of an antipsychotic, may become a valid alternative according to the model of amphetamine-induced psychosis.[49] Psychotic symptoms are associated with factors such as higher doses of bupropion, a history of bipolar disorder or psychosis, concomitant medications, for example, lithium or benzodiazepines, old age, or substance abuse.[47][50]
According to several case reports, stopping bupropion abruptly may result in a "discontinuation syndrome" expressed as dystonia, irritability, anxiety, mania, headache, aches and pains.[51] The prescribing information recommends dose tapering after bupropion has been used for seasonal affective disorder;[39] however it states that dose tapering is not required when discontinuing treatment for smoking cessation.[52]
Contraindications[edit]
GlaxoSmithKline advises that bupropion should not be prescribed to individuals with epilepsy or other conditions that lower the seizure threshold, such as anorexia nervosa, bulimia nervosa, active brain tumors, or concurrent alcohol and/or benzodiazepine use and/or withdrawal. It should be avoided in individuals who are also taking monoamine oxidase inhibitors (MAOIs). When switching from MAOIs to bupropion, it is important to include a washout period of about two weeks between the medications.[39] 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.[39]
Interactions[edit]
Since bupropion is metabolized to hydroxybupropion by the CYP2B6 enzyme, drug interactions with CYP2B6 inhibitors are possible: this includes medications like paroxetine, sertraline, fluoxetine, diazepam, clopidogrel, and orphenadrine. 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, phenobarbital, phenytoin and others.[53] Conversely, because bupropion is itself an inhibitor of CYP2D6 (Ki=21 μM),[1][54] as is its active metabolite, hydroxybupropion (Ki=13.3 μM), it can slow the clearance of other drugs metabolized by this enzyme.[1][2][3][5][53]
Bupropion lowers the threshold for epileptic seizures, and therefore can potentially interact with other medications that also lower it, such as theophylline, steroids, and some tricyclic antidepressants.[39] 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.[39]
Overdose[edit]
Bupropion is considered moderately dangerous in overdose.[55][56]
In the majority of childhood exploratory ingestions involving one or two tablets, children show no apparent symptoms.[57] In teenagers and adults seizures are more commonly observed, with the seizure rate increasing tenfold with doses of 600 mg daily.[58]
Bupropion overdose rarely results in death, although some cases have been reported. Symptoms include hallucinations and delusions, vomiting, aggressive behavior, seizures [59]
Pharmacology[edit]
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) sites by bupropion and its metabolites in the human brain as measured by positron emission tomography was 6–22% in an independent study[60] and 12–35% according to GlaxoSmithKline researchers.[61] 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. By contrast, approximately 65% occupancy or greater of DAT is required to achieve euphoria and reach abuse potential.[62] However, recent research indicates that dopamine is inactivated by norepinephrine reuptake in the frontal cortex, which largely lacks dopamine transporters, therefore bupropion can increase dopamine neurotransmission in this part of the brain, and this may be one possible explanation for any additional dopaminergic effects.[63]
Bupropion has also been shown to act as a noncompetitive nicotinic antagonist.[64]
Outside the nervous system, both bupropion and its primary metabolite hydrobupropion act in the liver as potent inhibitors of the enzyme CYP2D6, which metabolizes not only bupropion itself but also a variety of other drugs and biologically active substances.[54] This mechanism creates the potential for a variety of drug interactions.
Pharmacokinetics[edit]
Metabolites of bupropion.
Bupropion is metabolized in the liver by the cytochrome P450 isoenzyme CYP2B6.[36] 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. Pharmacological data on bupropion and its metabolites are shown in the table. Bupropion is known to weakly inhibit the α1 adrenergic receptor, with a 14% potency of its dopamine uptake inhibition, and the H1 receptor, with a 9% potency.[65]
Pharmacology of bupropion and its metabolites.[65][66][67][68][69]
| 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 |
| 5HT 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; 5HT = serotonin. |
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,[70] but discontinued development in 2006 due to "an unfavourable risk/benefit assessment".[71]
Bupropion is metabolized to hydroxybupropion by CYP2B6, an isozyme of the cytochrome P450 system. 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).[72] Based on this, some researchers have advocated monitoring of the blood level of bupropion and hydroxybupropion.[73]
There are significant interspecies differences in the metabolism of bupropion, with the metabolism in humans being more similar to guinea pigs than to mice and rats.[74] In fact hydroxybupropion, the main metabolite of bupropion in humans, is absent in rats.[75]
There have been two reported cases of false-positive urine amphetamine tests in persons taking bupropion. More specific follow-up tests were negative.[76][77]
Synthesis[edit]
Bupropion is a substituted cathinone. It is synthesized in two chemical steps starting from 3'-chloro-propiophenone. The alpha position adjacent to the ketone is first brominated followed by nucleophilic displacement of the resulting alpha-bromoketone with t-butylamine and treated with hydrochloric acid to give bupropion as the hydrochloride salt in 75–85% overall yield.[78][79]
Regulatory history[edit]
A bioequivalency profile comparison of 150 mg extended-release bupropion as produced by Impax Laboratories for Teva and Biovail for GlaxoSmithKline.
Bupropion was invented by Nariman Mehta of Burroughs Wellcome (now GlaxoSmithKline) in 1969, and the US patent for it was granted in 1974.[78] 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.[80] However, a significant incidence of epileptic seizures at the originally recommended dosage caused the withdrawal of the drug in 1986. Subsequently, the risk of seizures was found to be highly dose-dependent, and bupropion was re-introduced to the market in 1989 with a lower maximum recommended daily dose.[81]
In 1996, the FDA approved a sustained-release formulation of bupropion called Wellbutrin SR, intended to be taken twice a day (as compared with three times a day for immediate-release Wellbutrin).[82] In 2003, the FDA approved another sustained-release formulation called Wellbutrin XL, intended for once-daily dosing. Wellbutrin SR and XL are available in generic form in the United States, while in Canada, only the SR formulation is available in generic form. In 1997, bupropion was approved by the FDA for use as a smoking cessation aid under the name Zyban.[82] In 2006, Wellbutrin XL was similarly approved as a treatment for seasonal affective disorder.[83]
In April 2008, the FDA approved a formulation of bupropion as a hydrobromide salt instead of a hydrochloride salt, to be sold under the name Aplenzin by Sanofi-Aventis.[84]
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.[85] 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."[86] The FDA investigated these complaints and concluded that Budeprion XL is equivalent to Wellbutrin XL in regard to bioavailability of bupropion and its main active metabolite hydroxybupropion. The FDA also said that coincidental natural mood variation is the most likely explanation for the apparent worsening of depression after the switch from Wellbutrin XL to Budeprion XL.[87] On October 3, 2012, however, the FDA reversed this opinion, announcing that "Budeprion XL 300 mg fails to demonstrate therapeutic equivalence to Wellbutrin XL 300 mg."[88] The FDA did not test the bioequivalence of any of the other generic versions of Wellbutrin XL 300 mg, but requested that the four manufacturers submit data on this question to the FDA by March 2013.[88] As of October 2013 the FDA has made determinations on the formulations from some manufacturers not being bioequivalent. FDA Update from Oct 2013
In 2012, the U.S. Justice Department announced that GlaxoSmithKline had agreed to plead guilty and pay a $3-billion fine, in part for promoting the unapproved use of Wellbutrin for weight loss and sexual dysfunction.[89]
In France, marketing authorization was granted for Zyban on August 3, 2001, with a maximum daily dose of 300 mg;[90] only sustained-release bupropion is available, and only as a smoking cessation aid. 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.[91]
Recreational use[edit]
According to the US government classification of psychiatric medications, bupropion is "non-abusable".[92] In animal studies, squirrel monkeys and rats could be induced to self-administer bupropion, which is often taken as a sign of addiction potential; however, there are significant interspecies differences in bupropion metabolism.[54] There have been a number of anecdotal and case-study reports of bupropion abuse, but the bulk of evidence indicates that the subjective effects of bupropion are markedly different from those of addictive stimulants such as cocaine or amphetamine.[93]
References[edit]
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- ^ a b c d "Prexaton Bupropion hydrochloride PRODUCT INFORMATION". TGA eBusiness Services. Ascent Pharma Pty Ltd. 2 October 2012. Retrieved 22 October 2013.
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- ^ The INN originally assigned in 1974 by the World Health Organization was "amfebutamone". In 2000, the INN was reassigned as bupropion. See World Health Organization (2000). "International Nonproprietary Names for Pharmaceutical Substances (INN). Proposed INN: List 83" (PDF). WHO Drug Information 14 (2). Archived from the original on May 31, 2011. Retrieved June 22, 2009.
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External links[edit]
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Pharmacy and Pharmacology portal |
- Official Wellbutrin website
- List of international brand names for bupropion
- Bupropion on the Open Directory Project
- Wellbutrin Pharmacology, Pharmacokinetics, Studies, Metabolism – Bupropion – RxList Monographs
- NAMI Wellbutrin
- Bupropion article from mentalhealth.com
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Adrenergics
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Receptor ligands
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α1
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- Agonists: 5-FNE
- 6-FNE
- Amidephrine
- Anisodamine
- Anisodine
- Cirazoline
- Dipivefrine
- Dopamine
- Ephedrine
- Epinephrine
- Etilefrine
- Ethylnorepinephrine
- Indanidine
- Levonordefrin
- Metaraminol
- Methoxamine
- Methyldopa
- Midodrine
- Naphazoline
- Norepinephrine
- Octopamine
- Oxymetazoline
- Phenylephrine
- Phenylpropanolamine
- Pseudoephedrine
- Synephrine
- Tetrahydrozoline
Antagonists: Abanoquil
- Adimolol
- Ajmalicine
- Alfuzosin
- Amosulalol
- Arotinolol
- Atiprosin
- Benoxathian
- Buflomedil
- Bunazosin
- Carvedilol
- CI-926
- Corynanthine
- Dapiprazole
- DL-017
- Domesticine
- Doxazosin
- Eugenodilol
- Fenspiride
- GYKI-12,743
- GYKI-16,084
- Hydroxyzine
- Indoramin
- Ketanserin
- L-765,314
- Labetalol
- Mephendioxan
- Metazosin
- Monatepil
- Moxisylyte
- Naftopidil
- Nantenine
- Neldazosin
- Nicergoline
- Niguldipine
- Pelanserin
- Phendioxan
- Phenoxybenzamine
- Phentolamine
- Piperoxan
- Prazosin
- Quinazosin
- Ritanserin
- RS-97,078
- SGB-1,534
- Silodosin
- SL-89.0591
- Spiperone
- Talipexole
- Tamsulosin
- Terazosin
- Tibalosin
- Tiodazosin
- Tipentosin
- Tolazoline
- Trimazosin
- Upidosin
- Urapidil
- Zolertine
- Note that many TCAs, TeCAs, antipsychotics, ergolines, and some piperazines like buspirone and trazodone all antagonize α1-adrenergic receptors as well, which contributes to their side effects such as orthostatic hypotension.
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α2
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- Agonists: (R)-3-Nitrobiphenyline
- 4-NEMD
- 6-FNE
- Amitraz
- Apraclonidine
- Brimonidine
- Cannabivarin
- Clonidine
- Detomidine
- Dexmedetomidine
- Dihydroergotamine
- Dipivefrine
- Dopamine
- Ephedrine
- Ergotamine
- Epinephrine
- Esproquin
- Etilefrine
- Ethylnorepinephrine
- Guanabenz
- Guanfacine
- Guanoxabenz
- Levonordefrin
- Lofexidine
- Medetomidine
- Methyldopa
- Mivazerol
- Naphazoline
- Norepinephrine
- Oxymetazoline
- Phenylpropanolamine
- Piperoxan
- Pseudoephedrine
- Rilmenidine
- Romifidine
- Talipexole
- Tetrahydrozoline
- Tizanidine
- Tolonidine
- Urapidil
- Xylazine
- Xylometazoline
Antagonists: 1-PP
- Adimolol
- Aptazapine
- Atipamezole
- BRL-44408
- Buflomedil
- Cirazoline
- Efaroxan
- Esmirtazapine
- Fenmetozole
- Fluparoxan
- GYKI-12,743
- GYKI-16,084
- Idazoxan
- Mianserin
- Mirtazapine
- MK-912
- NAN-190
- Olanzapine
- Phentolamine
- Phenoxybenzamine
- Piperoxan
- Piribedil
- Rauwolscine
- Rotigotine
- SB-269,970
- Setiptiline
- Spiroxatrine
- Sunepitron
- Tolazoline
- Yohimbine
* Note that many atypical antipsychotics and azapirones like buspirone (via metabolite 1-PP) antagonize α2-adrenergic receptors as well.
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β
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Reuptake inhibitors
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NET
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- Selective norepinephrine reuptake inhibitors: Amedalin
- Atomoxetine (Tomoxetine)
- Ciclazindol
- Daledalin
- Edivoxetine
- Esreboxetine
- Lortalamine
- Mazindol
- Nisoxetine
- Reboxetine
- Talopram
- Talsupram
- Tandamine
- Viloxazine; Norepinephrine-dopamine reuptake inhibitors: Amineptine
- Bupropion (Amfebutamone)
- Fencamine
- Fencamfamine
- Lefetamine
- Levophacetoperane
- LR-5182
- Manifaxine
- Methylphenidate
- Nomifensine
- O-2172
- Radafaxine; Serotonin-norepinephrine reuptake inhibitors: Bicifadine
- Desvenlafaxine
- Duloxetine
- Eclanamine
- Levomilnacipran
- Milnacipran
- Sibutramine
- Venlafaxine; Serotonin-norepinephrine-dopamine reuptake inhibitors: Brasofensine
- Diclofensine
- DOV-102,677
- DOV-21,947
- DOV-216,303
- JNJ-7925476
- JZ-IV-10
- Methylnaphthidate
- Naphyrone
- NS-2359
- PRC200-SS
- SEP-225,289
- SEP-227,162
- Tesofensine; Tricyclic antidepressants: Amitriptyline
- Butriptyline
- Cianopramine
- Clomipramine
- Desipramine
- Dosulepin
- Doxepin
- Imipramine
- Lofepramine
- melitracen
- Nortriptyline
- Protriptyline
- Trimipramine; Tetracyclic antidepressants: Amoxapine
- Maprotiline
- Mianserin
- Oxaprotiline
- Setiptiline; Others: Cocaine
- CP-39,332
- Ethanol
- EXP-561
- Fezolamine
- Ginkgo biloba
- Indeloxazine
- Nefazodone
- Nefopam
- Pridefrine
- Tapentadol
- Tedatioxetine
- Teniloxazine
- Tofenacin
- Tramadol
- Ziprasidone
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VMAT
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- Ibogaine
- Reserpine
- Tetrabenazine
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Enzyme inhibitors
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Anabolism
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PAH
|
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|
|
TH
|
- 3-Iodotyrosine
- Aquayamycin
- Bulbocapnine
- Metirosine
- Oudenone
|
|
|
AAAD
|
- Benserazide
- Carbidopa
- DFMD
- Genistein
- Methyldopa
|
|
|
DBH
|
- Bupicomide
- Disulfiram
- Dopastin
- Fusaric acid
- Nepicastat
- Phenopicolinic acid
- Tropolone
|
|
|
PNMT
|
- CGS-19281A
- SKF-64139
- SKF-7698
|
|
|
|
Catabolism
|
|
MAO
|
- Nonselective: Benmoxin
- Caroxazone
- Echinopsidine
- Furazolidone
- Hydralazine
- Indantadol
- Iproclozide
- Iproniazid
- Isocarboxazid
- Isoniazid
- Linezolid
- Mebanazine
- Metfendrazine
- Nialamide
- Octamoxin
- Paraxazone
- Phenelzine
- Pheniprazine
- Phenoxypropazine
- Pivalylbenzhydrazine
- Procarbazine
- Safrazine
- Tranylcypromine; MAO-A selective: Amiflamine
- Bazinaprine
- Befloxatone
- Brofaromine
- Cimoxatone
- Clorgiline
- Eprobemide
- Esuprone
- Harmala alkaloids (Harmine,
- Harmaline
- Tetrahydroharmine
- Harman
- Norharman, etc)
- Methylene blue
- Metralindole
- Minaprine
- Moclobemide
- Pirlindole
- Sercloremine
- Tetrindole
- Toloxatone
- Tyrima; MAO-B selective:
- Ladostigil
- Lazabemide
- Milacemide
- Mofegiline
- Pargyline
- Rasagiline
- Safinamide
- Selegiline (also D-Deprenyl)
* Note that MAO-B inhibitors also influence norepinephrine/epinephrine levels since they inhibit the breakdown of their precursor dopamine.
|
|
|
COMT
|
- Entacapone
- Nitecapone
- Tolcapone
|
|
|
|
|
|
Others
|
|
|
Precursors
|
- L-Phenylalanine → L-Tyrosine → L-DOPA (Levodopa) → Dopamine
- L-DOPS (Droxidopa)
|
|
|
Cofactors
|
- Ferrous Iron (Fe2+)
- S-Adenosyl-L-Methionine
- Vitamin B3 (Niacin
- Nicotinamide → NADPH)
- Vitamin B6 (Pyridoxine
- Pyridoxamine
- Pyridoxal → Pyridoxal Phosphate)
- Vitamin B9 (Folic acid → Tetrahydrofolic acid)
- Vitamin C (Ascorbic acid)
- Zinc (Zn2+)
|
|
|
Others
|
- Activity enhancers: BPAP
- PPAP; Release blockers: Bethanidine
- Bretylium
- Guanadrel
- Guanazodine
- Guanclofine
- Guanethidine
- Guanoxan; Toxins: 6-OHDA
|
|
|
|
|
List of adrenergic drugs
|
|
|
Antidepressants (N06A)
|
|
|
Specific reuptake inhibitors (RIs), enhancers (REs), and releasing agents (RAs)
|
|
|
Selective serotonin reuptake inhibitors (SSRIs)
|
- Alaproclate
- Citalopram
- Escitalopram
- Femoxetine
- Fluoxetine#
- Fluvoxamine
- Indalpine
- Ifoxetine
- Litoxetine
- Omiloxetine
- Panuramine
- Paroxetine
- Pirandamine
- Seproxetine
- Sertraline
- Zimelidine‡
|
|
|
Serotonin–norepinephrine reuptake inhibitors (SNRIs)
|
- Clovoxamine
- Desvenlafaxine
- Duloxetine
- Levomilnacipran
- Eclanamine
- Milnacipran
- Sibutramine
- Venlafaxine
|
|
|
Serotonin–norepinephrine–dopamine reuptake inhibitors (SNDRIs)
|
- Adhyperforin
- Amitifadine
- Bicifadine
- Brasofensine
- BTS-74,398
- Cocaine
- Diclofensine
- DOV-102,677
- DOV-216,303
- EXP-561
- Fezolamine
- Hyperforin
- JNJ-7925476
- NS-2359
- PRC200-SS
- Pridefine
- SEP-225,289
- SEP-227,162
- Tesofensine
|
|
|
Norepinephrine reuptake inhibitors (NRIs)
|
- Amedalin
- Atomoxetine/Tomoxetine
- Binedaline
- Ciclazindol
- Daledalin
- Edivoxetine
- Esreboxetine
- Lortalamine
- Maprotiline
- Mazindol
- Nisoxetine
- Reboxetine
- Talopram
- Talsupram
- Tandamine
- Viloxazine
|
|
|
Dopamine reuptake inhibitors (DRIs)
|
|
|
|
Norepinephrine-dopamine reuptake inhibitors (NDRIs)
|
- Amineptine
- Bupropion/Amfebutamone
- Cilobamine
- Manifaxine
- Methylphenidate
- Nomifensine
- Radafaxine
- Tametraline
|
|
|
Norepinephrine-dopamine releasing agents (NDRAs)
|
- Amphetamine
- Befuraline
- Lisdexamfetamine
- Methamphetamine
- Phenethylamine
- Piberaline
- Tranylcypromine
|
|
|
Serotonin-norepinephrine-dopamine releasing agents (SNDRAs)
|
- 4-Methyl-αMT
- αET/Etryptamine
- αMT/Metryptamine
|
|
|
Selective serotonin reuptake enhancers (SSREs)
|
|
|
|
Others
|
- Indeloxazine
- Teniloxazine
- Tramadol
- Viqualine
|
|
|
|
|
Receptor antagonists and/or reuptake inhibitors
|
|
|
Serotonin antagonists and reuptake inhibitors (SARIs)
|
- Etoperidone
- Lubazodone
- Nefazodone
- Mepiprazole
- Trazodone
|
|
|
Noradrenergic and specific serotonergic antidepressants (NaSSAs)
|
- Aptazapine
- Esmirtazapine
- Mianserin
- Mirtazapine
- Setiptiline/Teciptiline
|
|
|
Norepinephrine-dopamine disinhibitors (NDDIs)
|
|
|
|
Serotonin modulators and stimulators (SMSs)
|
|
|
|
Others
|
|
|
|
|
|
Heterocyclic antidepressants (bi-, tri-, and tetracyclics)
|
|
|
Bicyclics
|
|
|
|
Tricyclics
|
- Amezepine
- Amineptine
- Amitriptyline#
- Amitriptylinoxide
- Azepindole
- Butriptyline
- Cianopramine
- Clomipramine#
- Cotriptyline
- Cyanodothiepin
- Demexiptiline
- Depramine/Balipramine
- Desipramine
- Dibenzepin
- Dimetacrine
- Dosulepin/Dothiepin
- Doxepin
- Enprazepine
- Fluotracen
- Hepzidine
- Homopipramol
- Imipramine
- Imipraminoxide
- Intriptyline
- Iprindole
- Ketipramine
- Litracen
- Lofepramine
- Losindole
- Mariptiline
- Melitracen
- Metapramine
- Mezepine
- Naranol
- Nitroxazepine
- Nortriptyline
- Noxiptiline
- Octriptyline
- Opipramol
- Pipofezine
- Propizepine
- Protriptyline
- Quinupramine
- Tampramine
- Tianeptine
- Tienopramine
- Trimipramine
|
|
|
Tetracyclics
|
- Amoxapine
- Aptazapine
- Azipramine
- Ciclazindol
- Ciclopramine
- Esmirtazapine
- Maprotiline
- Mazindol
- Mianserin
- Mirtazapine
- Oxaprotiline
- Setiptiline/Teciptiline
|
|
|
|
|
Monoamine oxidase inhibitors (MAOIs)
|
|
|
Nonselective
|
- Irreversible: Benmoxin
- Carbenzide
- Cimemoxin
- Domoxin
- Echinopsidine
- Iproclozide
- Iproniazid
- Isocarboxazid
- Mebanazine
- Metfendrazine
- Nialamide
- Octamoxin
- Phenelzine
- Pheniprazine
- Phenoxypropazine
- Pivalylbenzhydrazine
- Safrazine
- Tranylcypromine
- Reversible: Caroxazone
- Paraxazone
- Quercetin
|
|
|
MAOA-Selective
|
- Reversible: Amiflamine
- Bazinaprine
- Befloxatone
- Berberine
- Brofaromine
- Cimoxatone
- Esuprone
- Eprobemide
- Harmala Alkaloids (Harmine
- Harmaline
- Tetrahydroharmine
- Harman
- Norharman, etc)
- Methylene Blue
- Metralindole
- Minaprine
- Moclobemide
- Pirlindole
- Sercloremine
- Tetrindole
- Toloxatone
- Tyrima
|
|
|
MAOB-Selective
|
- Irreversible: Ladostigil
- Mofegiline
- Pargyline
- Rasagiline
- Selegiline
- Reversible: Lazabemide
- Milacemide
|
|
|
|
|
Azapirones and other 5-HT1A receptor agonists
|
|
- Alnespirone
- Aripiprazole
- Befiradol
- Buspirone
- Eptapirone
- Flesinoxan
- Flibanserin
- Gepirone
- Ipsapirone
- Oxaflozane
- Tandospirone
- Vilazodone
- Zalospirone
|
|
|
- #WHO-EM
- ‡Withdrawn from market
- Clinical trials:
- †Phase III
- §Never to phase III
|
|
|
|
|
dsrd (o, p, m, p, a, d, s), sysi/epon, spvo
|
proc (eval/thrp), drug (N5A/5B/5C/6A/6B/6D)
|
|
|
|
|
Antiaddictives (N07B)
|
|
Nicotine dependence/
(Nicotinic agonist) |
- Dianicline
- Varenicline
- Lobeline
- Mecamylamine
- Scopolamine
- NDRI (Bupropion)
- AA (Clonidine)
- CB1 (Surinabant)
|
|
| Alcohol dependence |
- AD inhibitor (Disulfiram
- Calcium carbimide)
- mGluR (Acamprosate)
- Opioid receptor antagonists (Naltrexone
- Nalmefene)
- Topiramate
- AA (Clonidine)
- Baclofen
|
|
| Opioid dependence |
- Buprenorphine
- Methadone
- Levacetylmethadol
- Dihydrocodeine
- Dihydroetorphine
- AA (Clonidine)
- Lofexidine
- Extended Release Morphine
- Extended Release Hydromorphone
- Baclofen
- Ibogaine
- Salvinorin A
|
|
| Stimulant dependence |
- Dextroamphetamine
- NDRI (Bupropion)
- DRI (Vanoxerine)
- Nocaine
- GABA analogue (Vigabatrin)
|
|
| Benzodiazepine dependence |
- AA (Clonidine)
- benzodiazepine (Diazepam)
- Phenytoin
- barbiturate (Phenobarbital)
|
|
| Cocaine dependence |
- NDRI (Bupropion)
- DRI (Vanoxerine)
- Nocaine
- Baclofen
- GABA analogue (Vigabatrin)
|
|
| Sedative-Hypnotic dependence |
- barbiturate (Phenobarbital)
- benzodiazepine (Diazepam
- Lorazepam)
- AA (Clonidine)
- Chloral hydrate
|
|
|
|
anat (n/s/m/p/4/e/b/d/c/a/f/l/g)/phys/devp
|
noco (m/d/e/h/v/s)/cong/tumr, sysi/epon, injr
|
proc, drug (N1A/2AB/C/3/4/7A/B/C/D)
|
|
|
|
|
Cholinergics
|
|
|
Receptor ligands
|
|
|
mAChR
|
- Agonists: 77-LH-28-1
- AC-42
- AC-260,584
- Aceclidine
- Acetylcholine
- AF30
- AF150(S)
- AF267B
- AFDX-384
- Alvameline
- AQRA-741
- Arecoline
- Bethanechol
- Butyrylcholine
- Carbachol
- CDD-0034
- CDD-0078
- CDD-0097
- CDD-0098
- CDD-0102
- Cevimeline
- Choline
- cis-Dioxolane
- Ethoxysebacylcholine
- LY-593,039
- L-689,660
- LY-2,033,298
- McNA343
- Methacholine
- Milameline
- Muscarine
- NGX-267
- Ocvimeline
- Oxotremorine
- PD-151,832
- Pilocarpine
- RS86
- Sabcomeline
- SDZ 210-086
- Sebacylcholine
- Suberylcholine
- Talsaclidine
- Tazomeline
- Thiopilocarpine
- Vedaclidine
- VU-0029767
- VU-0090157
- VU-0152099
- VU-0152100
- VU-0238429
- WAY-132,983
- Xanomeline
- YM-796
Antagonists: 3-Quinuclidinyl Benzilate
- 4-DAMP
- Aclidinium Bromide
- Anisodamine
- Anisodine
- Atropine
- Atropine Methonitrate
- Benactyzine
- Benzatropine/Benztropine
- Benzydamine
- BIBN 99
- Biperiden
- Bornaprine
- CAR-226,086
- CAR-301,060
- CAR-302,196
- CAR-302,282
- CAR-302,368
- CAR-302,537
- CAR-302,668
- CS-27349
- Cyclobenzaprine
- Cyclopentolate
- Darifenacin
- DAU-5884
- Dimethindene
- Dexetimide
- DIBD
- Dicyclomine/Dicycloverine
- Ditran
- EA-3167
- EA-3443
- EA-3580
- EA-3834
- Etanautine
- Etybenzatropine/Ethylbenztropine
- Flavoxate
- Himbacine
- HL-031,120
- Ipratropium bromide
- J-104,129
- Hyoscyamine
- Mamba Toxin 3
- Mamba Toxin 7
- Mazaticol
- Mebeverine
- Methoctramine
- Metixene
- N-Ethyl-3-Piperidyl Benzilate
- N-Methyl-3-Piperidyl Benzilate
- Orphenadrine
- Otenzepad
- Oxybutynin
- PBID
- PD-102,807
- PD-0298029
- Phenglutarimide
- Phenyltoloxamine
- Pirenzepine
- Piroheptine
- Procyclidine
- Profenamine
- RU-47,213
- SCH-57,790
- SCH-72,788
- SCH-217,443
- Scopolamine/Hyoscine
- Solifenacin
- Telenzepine
- Tiotropium bromide
- Tolterodine
- Trihexyphenidyl
- Tripitamine
- Tropatepine
- Tropicamide
- WIN-2299
- Xanomeline
- Zamifenacin; Others: 1st Generation Antihistamines (Brompheniramine
- chlorphenamine
- cyproheptadine
- dimenhydrinate
- diphenhydramine
- doxylamine
- mepyramine/pyrilamine
- phenindamine
- pheniramine
- tripelennamine
- triprolidine, etc)
- Tricyclic Antidepressants (Amitriptyline
- doxepin
- trimipramine, etc)
- Tetracyclic Antidepressants (Amoxapine
- maprotiline, etc)
- Typical Antipsychotics (Chlorpromazine
- thioridazine, etc)
- Atypical Antipsychotics (Clozapine
- olanzapine, etc.)
|
|
|
nAChR
|
- Agonists: 5-HIAA
- A-84,543
- A-366,833
- A-582,941
- A-867,744
- ABT-202
- ABT-418
- ABT-560
- ABT-894
- Acetylcholine
- Altinicline
- Anabasine
- Anatoxin-a
- AR-R17779
- Butinoline
- Butyrylcholine
- Carbachol
- Choline
- Cotinine
- Cytisine
- Decamethonium
- Desformylflustrabromine
- Dianicline
- Dimethylphenylpiperazinium
- Epibatidine
- Epiboxidine
- Ethanol
- Ethoxysebacylcholine
- EVP-4473
- EVP-6124
- Galantamine
- GTS-21
- Ispronicline
- Lobeline
- MEM-63,908/RG-3487
- Nicotine
- NS-1738
- PHA-543,613
- PHA-709,829
- PNU-120,596
- PNU-282,987
- Pozanicline
- Rivanicline
- RJR-2429
- Sazetidine A
- Sebacylcholine
- SIB-1508Y
- SIB-1553A
- SSR-180,711
- Suberylcholine
- Suxamethonium/Succinylcholine
- TC-1698
- TC-1734
- TC-1827
- TC-2216
- TC-5214
- TC-5619
- TC-6683
- Tebanicline
- Tropisetron
- UB-165
- Varenicline
- WAY-317,538
- XY-4083
Antagonists: 18-Methoxycoronaridine
- α-Bungarotoxin
- α-Conotoxin
- Alcuronium
- Amantadine
- Anatruxonium
- Atracurium
- Bupropion
- Chandonium
- Chlorisondamine
- Cisatracurium
- Coclaurine
- Coronaridine
- Dacuronium
- Decamethonium
- Dextromethorphan
- Dextropropoxyphene
- Dextrorphan
- Diadonium
- DHβE
- Dimethyltubocurarine/Metocurine
- Dipyrandium
- Dizocilpine/MK-801
- Doxacurium
- Duador
- Esketamine
- Fazadinium
- Gallamine
- Hexafluronium
- Hexamethonium/Benzohexonium
- Ibogaine
- Isoflurane
- Ketamine
- Kynurenic acid
- Laudexium/Laudolissin
- Levacetylmethadol
- Malouetine
- Mecamylamine
- Memantine
- Methadone (Levomethadone)
- Methorphan/Racemethorphan
- Methyllycaconitine
- Metocurine
- Mivacurium
- Morphanol/Racemorphan
- Neramexane
- Nitrous Oxide
- Pancuronium
- Pempidine
- Pentamine
- Pentolinium
- Phencyclidine
- Pipecuronium
- Radafaxine
- Rapacuronium
- Rocuronium
- Surugatoxin
- Thiocolchicoside
- Toxiferine
- Trimethaphan
- Tropeinium
- Tubocurarine
- Vecuronium
- Xenon
|
|
|
|
|
Reuptake inhibitors
|
|
|
Plasmalemmal
|
|
CHT Inhibitors
|
- Hemicholinium-3/Hemicholine
- Triethylcholine
|
|
|
|
Vesicular
|
|
|
|
|
|
Enzyme inhibitors
|
|
|
Anabolism
|
|
ChAT inhibitors
|
- 1-(-Benzoylethyl)pyridinium
- 2-(α-Naphthoyl)ethyltrimethylammonium
- 3-Chloro-4-stillbazole
- 4-(1-Naphthylvinyl)pyridine
- Acetylseco hemicholinium-3
- Acryloylcholine
- AF64A
- B115
- BETA
- CM-54,903
- N,N-Dimethylaminoethylacrylate
- N,N-Dimethylaminoethylchloroacetate
|
|
|
|
Catabolism
|
|
AChE inhibitors
|
|
|
|
BChE inhibitors
|
- Cymserine * Many of the acetylcholinesterase inhibitors listed above act as butyrylcholinesterase inhibitors.
|
|
|
|
|
|
Others
|
|
|
Precursors
|
- Choline (Lecithin)
- Citicoline
- Cyprodenate
- Dimethylethanolamine
- Glycerophosphocholine
- Meclofenoxate/Centrophenoxine
- Phosphatidylcholine
- Phosphatidylethanolamine
- Phosphorylcholine
- Pirisudanol
|
|
|
Cofactors
|
- Acetic acid
- Acetylcarnitine
- Acetyl-coA
- Vitamin B5 (Pantethine
- Pantetheine
- Panthenol)
|
|
|
Others
|
- Acetylcholine releasing agents: α-Latrotoxin
- β-Bungarotoxin; Acetylcholine release inhibitors: Botulinum toxin (Botox); Acetylcholinesterase reactivators: Asoxime
- Obidoxime
- Pralidoxime
|
|
|
|
|
Dopaminergics
|
|
|
Receptor ligands
|
|
|
Agonists
|
- Adamantanes: Amantadine
- Memantine
- Rimantadine; Aminotetralins: 7-OH-DPAT
- 8-OH-PBZI
- Rotigotine
- UH-232; Benzazepines: 6-Br-APB
- Fenoldopam
- SKF-38,393
- SKF-77,434
- SKF-81,297
- SKF-82,958
- SKF-83,959; Ergolines: Bromocriptine
- Cabergoline
- Dihydroergocryptine
- Epicriptine
- Lisuride
- LSD
- Pergolide; Dihydrexidine derivatives: 2-OH-NPA
- A-86,929
- Ciladopa
- Dihydrexidine
- Dinapsoline
- Dinoxyline
- Doxanthrine; Others: A-68,930
- A-77636
- A-412,997
- ABT-670
- ABT-724
- Aplindore
- Apomorphine
- Aripiprazole
- Bifeprunox
- BP-897
- CY-208,243
- Dizocilpine
- Etilevodopa
- Flibanserin
- Ketamine
- Melevodopa
- Modafinil
- Pardoprunox
- Phencyclidine
- PD-128,907
- PD-168,077
- PF-219,061
- Piribedil
- Pramipexole
- Propylnorapomorphine
- Pukateine
- Quinagolide
- Quinelorane
- Quinpirole
- RDS-127
- Ro10-5824
- Ropinirole
- Rotigotine
- Roxindole
- Salvinorin A
- SKF-89,145
- Sumanirole
- Terguride
- Umespirone
- WAY-100,635
|
|
|
Antagonists
|
- Typical antipsychotics: Acepromazine
- Azaperone
- Benperidol
- Bromperidol
- Clopenthixol
- Chlorpromazine
- Chlorprothixene
- Droperidol
- Flupentixol
- Fluphenazine
- Fluspirilene
- Haloperidol
- Levosulpiride
- Loxapine
- Mesoridazine
- Methotrimeprazine
- Nemonapride
- Penfluridol
- Perazine
- Periciazine
- Perphenazine
- Pimozide
- Prochlorperazine
- Promazine
- Sulforidazine
- Sulpiride
- Sultopride
- Thioridazine
- Thiothixene
- Trifluoperazine
- Triflupromazine
- Trifluperidol
- Zuclopenthixol; Atypical antipsychotics: Amisulpride
- Asenapine
- Blonanserin
- Cariprazine
- Carpipramine
- Clocapramine
- Clorotepine
- Clozapine
- Gevotroline
- Iloperidone
- Lurasidone
- Melperone
- Molindone
- Mosapramine
- Olanzapine
- Paliperidone
- Perospirone
- Piquindone
- Quetiapine
- Remoxipride
- Risperidone
- Sertindole
- Tiospirone
- Zicronapine
- Ziprasidone
- Zotepine; Antiemetics: AS-8112
- Alizapride
- Bromopride
- Clebopride
- Domperidone
- Metoclopramide
- Thiethylperazine; Others: Amoxapine
- Buspirone
- Butaclamol
- Ecopipam
- EEDQ
- Eticlopride
- Fananserin
- Hydroxyzine
- L-745,870
- Nafadotride
- Nuciferine
- PNU-99,194
- Raclopride
- Sarizotan
- SB-277,011-A
- SCH-23,390
- SKF-83,959
- Sonepiprazole
- Spiperone
- Spiroxatrine
- Stepholidine
- Tetrahydropalmatine
- Tiapride
- UH-232
- Yohimbine
|
|
|
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Reuptake inhibitors
|
|
|
Plasmalemmal
|
|
DAT inhibitors
|
- Piperazines: DBL-583
- GBR-12,935
- Nefazodone
- Vanoxerine; Piperidines: BTCP
- Desoxypipradrol
- Dextromethylphenidate
- Difemetorex
- Ethylphenidate
- Methylnaphthidate
- Methylphenidate
- Phencyclidine
- Pipradrol; Pyrrolidines: Diphenylprolinol
- MDPV
- Naphyrone
- Prolintane
- Pyrovalerone; Tropanes: Altropane
- Brasofensine
- CFT
- Cocaine
- Dichloropane
- Difluoropine
- FE-β-CPPIT
- FP-β-CPPIT
- Ioflupane (123I)
- Iometopane
- RTI-112
- RTI-113
- RTI-121
- RTI-126
- RTI-150
- RTI-177
- RTI-229
- RTI-336
- Tenocyclidine
- Tesofensine
- Troparil
- Tropoxane
- WF-11
- WF-23
- WF-31
- WF-33; Others: Adrafinil
- Armodafinil
- Amfonelic acid
- Amphetamine
- Amineptine
- Benzatropine
- Bromantane
- BTQ
- BTS-74,398
- Bupropion
- Ciclazindol
- Diclofensine
- Dimethocaine
- Diphenylpyraline
- Dizocilpine
- DOV-102,677
- DOV-21,947
- DOV-216,303
- Etybenzatropine
- EXP-561
- Fencamine
- Fencamfamine
- Fezolamine
- Fluorenol
- GYKI-52,895
- Indatraline
- Ketamine
- Lefetamine
- Levophacetoperane
- LR-5182
- Manifaxine
- Mazindol
- Medifoxamine
- Mesocarb
- Modafinil
- Nefopam
- Nomifensine
- NS-2359
- O-2172
- Pridefrine
- Propylamphetamine
- Radafaxine
- SEP-225,289
- SEP-227,162
- Sertraline
- Sibutramine
- Tametraline
- Tedatioxetine
- Tripelennamine
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Vesicular
|
|
VMAT inhibitors
|
- Deserpidine
- Ibogaine
- Reserpine
- Tetrabenazine
|
|
|
|
|
|
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|
|
Allosteric modulators
|
|
- Quinazolinamines: SoRI-9804
- SoRI-20040
- SoRI-20041
|
|
|
|
Enzyme inhibitors
|
|
|
Anabolism
|
|
PAH inhibitors
|
|
|
|
TH inhibitors
|
- 3-Iodotyrosine
- Aquayamycin
- Bulbocapnine
- Metirosine
- Oudenone
|
|
|
AAAD/DDC inhibitors
|
- Benserazide
- Carbidopa
- DFMD
- Genistein
- Methyldopa
|
|
|
|
Catabolism
|
|
MAO inhibitors
|
- Nonselective: Benmoxin
- Caroxazone
- Echinopsidine
- Furazolidone
- Hydralazine
- Indantadol
- Iproclozide
- Iproniazid
- Isocarboxazid
- Isoniazid
- Linezolid
- Mebanazine
- Metfendrazine
- Nialamide
- Octamoxin
- Paraxazone
- Phenelzine
- Pheniprazine
- Phenoxypropazine
- Pivalylbenzhydrazine
- Procarbazine
- Safrazine
- Tranylcypromine; MAO-A selective: Amiflamine
- Bazinaprine
- Befloxatone
- Brofaromine
- Cimoxatone
- Clorgiline
- Eprobemide
- Esuprone
- Harmala alkaloids
- Methylene Blue
- Metralindole
- Minaprine
- Moclobemide
- Pirlindole
- Sercloremine
- Tetrindole
- Toloxatone
- Tyrima; MAO-B selective: D-Deprenyl
- Ethanol
- L-Deprenyl (Selegiline)
- Ladostigil
- Lazabemide
- Milacemide
- Nicotine
- Pargyline
- Rasagiline
- Safinamide
|
|
|
COMT inhibitors
|
- Entacapone
- Nitecapone
- Tolcapone
|
|
|
DBH inhibitors
|
- Disulfiram
- Dopastin
- Fusaric acid
- Nepicastat
- Tropolone
|
|
|
|
|
|
Others
|
|
|
Precursors
|
- L-Phenylalanine → L-Tyrosine → L-DOPA (Levodopa)
|
|
|
Cofactors
|
- Ferrous iron (Fe2+)
- Tetrahydrobiopterin
- Vitamin B3 (Niacin
- Nicotinamide → NADPH)
- Vitamin B6 (Pyridoxine
- Pyridoxamine
- Pyridoxal → Pyridoxal phosphate)
- Vitamin B9 (Folic acid → Tetrahydrofolic acid)
- Vitamin C (Ascorbic acid)
- Zinc (Zn2+)
|
|
|
Others
|
- Activity enhancers: BPAP * PPAP; Toxins: 6-OHDA; Steroids: Anabolic-androgenic steroids
|
|
|
|
|
List of dopaminergic drugs
|
|
|
GlaxoSmithKline
|
|
| Subsidiaries |
- GlaxoSmithKline Pakistan
- GlaxoSmithKline Pharmaceuticals Ltd
- Stiefel Laboratories
- ViiV Healthcare (85%)
|
|
Predecessors and fully
integrated acquisitions |
- Allen & Hanburys
- Beecham Group
- Block Drug
- Burroughs Wellcome
- Glaxo
- Glaxo Wellcome
- Human Genome Sciences
- Recherche et Industrie Thérapeutiques
- SmithKline Beecham
- Smith, Kline & French
|
|
Products
(List) |
|
Current
|
|
Pharmaceuticals
|
- Advair
- Albenza
- Alli
- Amerge
- Amoxil
- Arixtra
- Arranon/Atriance
- Augmentin
- Avamys/Veramyst
- Avandia
- Avodart
- AZT1
- Beconase
- Boniva
- Ceftin
- Combivir1
- Coreg
- Dexedrine
- Dyazide
- Epivir/Epivir-HBV/Heptovir/Zeffix1
- Flixonase
- Imitrex/Treximet
- Jayln
- Lamictal
- Lanoxin
- Levitra2
- Lovaza
- Parnate
- Paxil/Seroxat/Aropax
- Promacta
- Relenza
- Requip
- Rescriptor1
- Serlipet
- Tagamet
- Treximet
- Trizivir1
- Tykerb/Tyverb
- Valtrex/Zelitrex
- Ventolin HFA
- Viracept1
- Wellbutrin
- Zantac
- Ziagen1
- Zofran
- Zovirax
|
|
|
Vaccines
|
- Hepatyrix
- Pandemrix
- Twinrix
|
|
|
Other
|
- Aquafresh
- Boost
- Eno
- Horlicks
- Lucozade
- Maxinutrition
- Nicoderm
- Nicorette
- NiQuitin
- Panadol
- Panadol night
- Ralgex
- Ribena
- Sensodyne
- Solpadeine
- Synthol
- Tums
|
|
|
|
Former
|
- BC Powder
- Geritol
- Goody's Powder
|
|
|
| People |
|
Current directors
|
- Chris Gent
- Andrew Witty
- Roy Anderson
- Stephanie Burns
- Stacey Cartwright
- Lawrence Culp
- Crispin Davis
- Simon Dingemans
- Judy Lewent
- Deryck Maughan
- James Murdoch
- Daniel Podolsky
- Moncef Slaoui
- Tom de Swaan
- Robert Wilson
|
|
|
Other
|
- Thomas Beecham
- Silas M. Burroughs
- Mahlon Kline
- John K. Smith
- Henry Wellcome
|
|
|
| Other |
- Canada v. GlaxoSmithKline Inc.
- GlaxoSmithKline Prize
- Side Effects
- United States v. GlaxoSmithKline
|
|
- 1Products of ViiV Healthcare 2Co-marketed with Bayer Pharmaceuticals
|
|