Ondansetron
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|
| Systematic (IUPAC) name |
| (RS)-9-methyl-3-[(2-methyl-1H-imidazol-1-yl)methyl]-2,3-dihydro-1H-carbazol-4(9H)-one |
| Clinical data |
| Trade names |
Zofran Ondisolv |
| AHFS/Drugs.com |
monograph |
| MedlinePlus |
a601209 |
| Pregnancy cat. |
B1 (AU) B (US) |
| Legal status |
Prescription Only (S4) (AU) ℞-only (US) |
| Routes |
Oral, rectal, IV, IM |
| Pharmacokinetic data |
| Bioavailability |
~60% |
| Protein binding |
70%-76% |
| Metabolism |
Hepatic (CYP3A4, CYP1A2, CYP2D6) |
| Half-life |
5.7 hours |
| Excretion |
Renal |
| Identifiers |
| CAS number |
99614-02-5 Y |
| ATC code |
A04AA01 |
| PubChem |
CID 4595 |
| IUPHAR ligand |
2290 |
| DrugBank |
DB00904 |
| ChemSpider |
4434 Y |
| UNII |
4AF302ESOS Y |
| KEGG |
D00456 Y |
| ChEMBL |
CHEMBL46 Y |
| Chemical data |
| Formula |
C18H19N3O |
| Mol. mass |
293.4 g/mol |
SMILES
- O=C3c2c1ccccc1n(c2CCC3Cn4ccnc4C)C
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InChI
-
InChI=1S/C18H19N3O/c1-12-19-9-10-21(12)11-13-7-8-16-17(18(13)22)14-5-3-4-6-15(14)20(16)2/h3-6,9-10,13H,7-8,11H2,1-2H3 Y
Key:FELGMEQIXOGIFQ-UHFFFAOYSA-N Y
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Y (what is this?) (verify)
|
Ondansetron (INN) (//; developed and first marketed by GlaxoSmithKline as Zofran) is a serotonin 5-HT3 receptor antagonist used mainly as an antiemetic (to treat nausea and vomiting), often following chemotherapy. It affects both peripheral and central nerves.[1] Ondansetron reduces the activity of the vagus nerve, which deactivates the vomiting center in the medulla oblongata, and also blocks serotonin receptors in the chemoreceptor trigger zone. It has little effect on vomiting caused by motion sickness, and does not have any effect on dopamine receptors or muscarinic receptors.
Contents
- 1 Clinical uses
- 1.1 Investigational and off-label
- 1.1.1 Neuropsychiatric disorders
- 1.1.2 Substance use
- 1.1.3 Irritable bowel syndrome
- 1.1.4 Postanesthetic shivering
- 2 Adverse effects
- 3 History
- 4 Brand names
- 5 Publication bias
- 6 References
- 7 External links
Clinical uses[edit]
See also: 5-HT3 antagonist
The 5-HT3 receptor antagonists are the primary drugs used to treat and prevent chemotherapy-induced nausea and vomiting (CINV). A common use case is to give them intravenously about 30 minutes before commencement of a chemotherapy treatment. Ondansetron is also effective in controlling post-operative nausea and vomiting (PONV) and post-radiation nausea and vomiting, and is a possible therapy for nausea and vomiting due to acute or chronic medical illness or acute gastroenteritis.
Although it is highly effective, the high cost of the brand-name version had limited its use to controlling PONV and CINV.[2] It is also used off-label to treat hyperemesis gravidarum in pregnant women, but there is no conclusive data available on its safety in pregnancy, especially during the first trimester. It is also used to treat cyclic vomiting syndrome; although there have been no formal trials to confirm efficacy, case reports suggests it can be helpful in some cases. The drug is administered 1–3 times daily, depending on the severity of nausea and/or vomiting. The normal oral dose for adults and children over the age of 12 is 8 mg initially, followed by a second dose of 8 mg eight hours later. The drug is then administered once every 12 hours, usually for not more than 2–3 days. Following oral administration, it takes about 1.5 to 2 hours to reach maximum plasma concentrations. This drug is removed from the body by the liver and kidneys.
The clinical effect of ondansetron (and other drugs from the same group) can be potentiated by combining it with dexamethasone.
Investigational and off-label[edit]
During the past decade ondansetron has been increasingly used in the United States for Nausea and Vomiting of Pregnancy (NVP), owing to the lack of a drug approved by the U.S. Food and Drug Administration (FDA) for this condition (see also Hyperemesis gravidarum). While fetal safety data for doxylamine-pyridoxine are based on more than a quarter of a million pregnancies, the fetal safety data for ondansetron are based on fewer than 200 births. Moreover, a recent case-control study suggested there was an increased risk of cleft palate associated with ondansetron. Recently, the FDA issued a warning about potentially serious QT prolongation and torsade de pointes associated with ondansetron use; the warning included a list of precautions and tests that must be followed. The drug is not labeled for use in NVP in either the United States or Canada. Based on the data available today, ondansetron use cannot be assumed to be safe during pregnancy.[3]
A small study raised concern about Zofran increasing the risk of cleft palate. Since then a much larger study has eased concerns in this area. The new study of more than 600,000 pregnancies in Denmark found no evidence of major birth-related problems. References to this study: http://www.parents.com/blogs/parents-news-now/2013/03/01/pregnancy/anti-nausea-drug-safe-for-pregnancy-study-finds/ http://www.usatoday.com/story/news/nation/2013/02/27/pregnancy-nausea-drug-fetus/1952181/ http://www.huffingtonpost.com/2013/02/27/zofran-pregnancy_n_2776753.html http://www.aboutlawsuits.com/zofran-pregnancy-study-no-risk-defects-41919/
Neuropsychiatric disorders[edit]
A 2006 double-blind, randomized controlled trial indicated that ondansetron may have value in the treatment of schizophrenia, as an adjunct to haloperidol. The study found the combination to significantly improve negative schizophrenia symptoms, and people taking both drugs experienced fewer of the adverse effects commonly associated with haloperidol.[4] An earlier, smaller, open-label trial had found ondansetron to be useful in treating antipsychotic-induced tardive dyskinesia in people with schizophrenia, and the study patients also showed significant improvement in the disease's symptoms.[5][6]
Early studies have also examined ondansetron as a possible treatment for psychosis resulting from advanced Parkinson's disease.[7] Its apparent benefits despite a lack of any significant antagonistic properties at dopamine receptors or the 5-HT2A receptor raises interesting questions about the etiology of psychosis.
Hewlett and others found that the treatment of obsessive compulsive disorder with Ondansetron 1 mg three times daily was associated with a significant decrease in the Yale Brown Obsessive Compulsive scores in a small (n=8), 8-week, open-label study.[8]
Substance use[edit]
Ondansetron lowers the cravings for alcohol, especially in early-onset alcoholics. In one cognitive-behavioral therapy study, ondansetron patients with early-onset alcoholism had fewer drinks per day and reported more days without drinking at all, as compared to the other groups in the study. Also of note, individuals with the LL genotype show significant improvements in alcohol misuse when treated with ondansetron, compared with individuals with the other genotypes of the 5HTTLPR polymorphism, who showed no improvement over placebo.[9][10][11]
Researchers at the Stanford University School of Medicine have demonstrated that ondansetron might be useful and effective for treating withdrawal symptoms of opioid addictions.[12] Unlike the existing treatments methadone and buprenorphine, it is not itself an opioid.[12] Additionally, it does not require continued supervision like treatment with clonidine.[12]
The original experiment used mice who were injected with increasing doses of morphine, assayed with naloxone and then underwent haplotypic analysis to isolate a gene candidate.[13] HTR3A which codes for the 5-HT3 receptor emerged as the primary candidate, which suggested 5-HT3 antagonist ondansetron as a possible treatment.[13] The researchers were then able to show using an acute morphine administration model the efficacy in withdrawal symptom control in humans.[13]
Irritable bowel syndrome[edit]
Ondansetron blocks the 5-HT3 receptor in the enteric nervous system, and thereby reduces colonic contractions, sensory perception, and motility. A large number of drugs in this category, 5-HT3 antagonists, have been shown to have this effect, which positively impacts irritable bowel syndrome with diarrhea (IBS-D). Thus, ondansetron has been effective in treating diarrhea-predominant IBS in initial studies, and is being used off label for this exact effect.[14]
Postanesthetic shivering[edit]
Two small, placebo-controlled trials have been conducted to assess the efficacy of ondansetron for postanesthetic shivering, a common occurrence after surgery. Ondansetron was found to be as effective as pethidine (meperidine, Demerol) when given as a single IV dose before anesthesia.[15]
Adverse effects[edit]
Ondansetron is a well-tolerated drug with few side effects. Constipation, dizziness and headache are the most commonly reported side effects associated with its use. There have been no significant drug interactions reported with this drug's use. It is broken down by the hepatic cytochrome P450 system and it has little effect on the metabolism of other drugs broken down by this system.
On September 15, 2011, the U.S. FDA issued a Medwatch Safety Alert for Zofran (ondansetron) in patients with congenital Long QT syndrome, a heart arrhythmia. The FDA further required GlaxoSmithKline to conduct a thorough QT study to determine the degree to which Zofran may cause QT interval prolongation.[16] On June 29, 2012, the FDA issued a Drug Safety Communication Update entitled New information regarding QT prolongation with ondansetron (Zofran).[17] Ondansetron was included in the List of Potential Signals of Serious Risks/New Safety Information Identified by the FDA Adverse Event Reporting System (FAERS) between January– March 2013.[18] As a result of these concerns, the rarely prescribed 32-mg dose of ondansetron (Zofran) was voluntarily removed from the market in December, 2012.[19][20]
History[edit]
A vial of Zofran for intravenous injection
Ondansetron was developed around 1984 by scientists working at Glaxo's laboratories in London. It is in both the imidazole and carbazole families of heterocyclic compounds. After several attempts the company successfully filed for U.S. patent protection for the drug in 1986. U.S. Patent 4,695,578 was granted in September 1987 while U.S. Patent 4,753,789 was granted in June 1988. U.S. Patent 5,578,628, a divisional patent of U.S. Patent 4,753,789, was granted on November 26, 1996. Ondansetron was granted FDA approval as Zofran in January 1991. Glaxo did pediatric research on Zofran's uses, and gained a patent extension as a result, extending U.S. exclusivity until December 24, 2006. The FDA subsequently approved the first generic versions in December 2006, with marketing approval granted to Teva Pharmaceuticals USA and SICOR Pharmaceuticals.
Brand names[edit]
Ondansetron is marketed by GlaxoSmithKline (GSK) under the trade name Zofran. Other manufacturers include Pfizer Injectables (Ondanzetron), Opsonin Pharma Bangladesh (Anset), Strativa Pharmaceuticals (Zuplenz), Indswift Ltd. (Ondisolv), Cipla Ltd. (Emeset), Gedeon Richter Ltd. (Emetron), Korea United Pharmaceuticals (Emodan), Zentiva a.s. (Ondemet), Strides Arcolab (Setronax), Emistat (Unimed and Unihealth Bangladesh Ltd.) Glenmark Generics Ltd. (India) (Ondansetron) and Novell Pharmaceutical Laboratories (Ondavell). On May 29, 2006, Baxter Healthcare received tentative approval[21] to market its own label of Ondansetron Injection, USP, 8 mg/50 mL and 32 mg/50 mL iso-osmotic sodium chloride solution, beginning upon expiration of GSK's patent later that year.
Publication bias[edit]
In 1997, ondansetron was the subject of a meta-analysis case-study published in the British Medical Journal. Researchers examined 84 trials, with 11,980 patients receiving ondansetron, published between 1991 and September 1996. Intravenous ondansetron 4 mg versus placebo was investigated in 16 reports and three further reports which had been duplicated six times. The number needed to treat (NNT) to prevent vomiting within 24 hours was 9.5, with 95% confidence interval 6.9 to 15, in the 16 non-duplicated reports. In the three duplicated reports, the NNT was significantly lower at 3.9 (3.3 to 4.8) with P<0.00001. When all 25 reports were combined the apparent number needed to treat improved to 4.9 (4.4 to 5.6). Inclusion of duplicate reports led to a 23% overestimation of ondansetron's antiemetic efficacy.[22]
In addition, the authors found that the covert duplication of reports on ondansetron was not easy to detect, because of lack of cross-referencing between papers, and that reports containing duplicate findings were cited in eight reviews of the drug.[22] Their analysis was a subject of an editorial in the Journal of the American Medical Association in 1999.[23]
References[edit]
- ^ Jiang-Hong Ye et al. "Ondansetron: A Selective 5-HT3 Receptor Antagonist and Its Applications in CNS-Related Disorders" (PDF). doi:10.1111/j.1527-3458.2001.tb00195.x
- ^ Cooke, C. E.; Mehra, I. V. (1994). "Oral ondansetron for preventing nausea and vomiting". American journal of hospital pharmacy 51 (6): 762–771. PMID 8010314. edit
- ^ Koren, G (2012 Oct). "Motherisk update. Is ondansetron safe for use during pregnancy?". Canadian family physician Medecin de famille canadien 58 (10): 1092–3. PMID 23064917.
- ^ Zhang ZJ, Kang WH, Li Q, Wang XY, Yao SM, Ma AQ (2006). "Beneficial effects of ondansetron as an adjunct to haloperidol for chronic, treatment-resistant schizophrenia: a double-blind, randomized, placebo-controlled study". Schizophrenia Research 88 (1–3): 102–10. doi:10.1016/j.schres.2006.07.010. PMID 16959472.
- ^ Zullino DF, Eap CB, Voirol P (2001). "Ondansetron for tardive dyskinesia". Am J Psychiatry 158 (4): 657–8. doi:10.1176/appi.ajp.158.4.657-a. PMID 11282718.
- ^ Sirota P, Mosheva T, Shabtay H, Giladi N, Korczyn AD (2000). "Use of the selective serotonin 3 receptor antagonist ondansetron in the treatment of neuroleptic-induced tardive dyskinesia". Am J Psychiatry 157 (2): 287–9. doi:10.1176/appi.ajp.157.2.287. PMID 10671405. Free full text
- ^ Zoldan J, Friedberg G, Livneh M, Melamed E (1995). "Psychosis in advanced Parkinson's disease: treatment with ondansetron, a 5-HT3 receptor antagonist". Neurology 45 (7): 1305–8. PMID 7617188.
- ^ Hewlett WA, Schmid SP, Salomon RM (2003). "Pilot trial of ondansetron in the treatment of 8 patients with obsessive compulsive disorder". J Clin Psychiatry 64 (9): 1025–30. doi:10.4088/JCP.v64n0907. PMID 14628977.
- ^ "Ondansetron can prevent alcohol craving". June 11, 2006. Retrieved 2007-11-05.
- ^ Sellers EM, Toneatto T, Romach MK, Somer GR, Sobell LC, Sobell MB (1994). "Clinical efficacy of the 5-HT3 antagonist ondansetron in alcohol abuse and dependence". Alcohol Clin Exp Res 18 (4): 879–85. doi:10.1111/j.1530-0277.1994.tb00054.x. PMID 7978099.
- ^ "Genes Predict Success of Ondansetron Treatment for Alcoholism". January 25, 2011. Retrieved 2011-01-25.
- ^ a b c "Stanford scientists identify drug to treat opioid addiction". 17 FEB 2009. Retrieved 19 FEB 2009.
- ^ a b c Chu LF, Liang DY, Li X, Sahbaie P, Dʼarcy N, Liao G, Peltz G, David Clark J (February 2009). "From mouse to man: the 5-HT3 receptor modulates physical dependence on opioid narcotics". Pharmacogenet. Genomics 19 (3): 193–205. doi:10.1097/FPC.0b013e328322e73d. PMC 2730361. PMID 19214139.
- ^ Future for IBS; Medicinenet Article
- ^ Generali JA, Cada DJ (August 2009). "Ondansetron: postanesthetic shivering". Hospital Pharmacy 44 (8): 670–1.
- ^ "Zofran (ondansetron): Drug Safety Communication - Risk of Abnormal Heart Rhythms". U.S. Food and Drug Administration. 9/15/2011. Retrieved 2013-08-18.
- ^ "FDA Drug Safety Communication: New information regarding QT prolongation with ondansetron (Zofran)". U.S. Food and Drug Administration. 06-29-2012. Retrieved 2013-08-18.
- ^ "Potential Signals of Serious Risks/New Safety Information Identified by the FDA Adverse Event Reporting System (FAERS) between January– March 2013". U.S. Food and Drug Administration. 05/15/2013. Retrieved 2013-08-18.
- ^ "FDA Drug Safety Communication: Updated information on 32 mg intravenous ondansetron (Zofran) dose and pre-mixed ondansetron products". U.S. Food and Drug Administration. 12-4-2012. Retrieved 2013-08-18. "The U.S. Food and Drug Administration (FDA) is notifying health care professionals that the 32 mg, single intravenous (IV) dose of the anti-nausea drug Zofran (ondansetron hydrochloride) will no longer be marketed because of the potential for serious cardiac risks. This dose has been removed from the Zofran drug label."
- ^ Frieden, Joyce (Dec 4, 2012). "High-Dose Zofran Pulled From Market". Medpage Today. Retrieved 2013-08-18.
- ^ "Center for Drug Evaluation & Research (FDA) letter of tentative approval for Ondansetron NDA by Baxter Healthcare Corp" (PDF).
- ^ a b Tramèr, Martin R.; D. John M. Reynolds, R. Andrew Moore, Henry J. McQuay (13 September 1997). "Impact of covert duplicate publication on meta-analysis: a case study". British Medical Journal. doi:10.1136/bmj.315.7109.635. Retrieved 10 December 2012.
- ^ Rennie, Drummond (10 November 1999). "Fair Conduct and Fair Reporting of Clinical Trials". The Journal of the American Medical Association 282 (18): 1766–1768. doi:10.1001/jama.282.18.1766. Retrieved 10 December 2012.
External links[edit]
- U.S. National Library of Medicine: Drug Information Portal - Ondansetron
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- Olanzapine
- Paliperidone
- Pimozide
- Quetiapine
- Risperidone
- Sertindole
- Ziprasidone
- Zotepine; Typical antipsychotics: Chlorpromazine
- Loxapine
- Pipamperone; Antidepressants: Agomelatine
- Amitriptyline
- Amoxapine
- Aptazapine
- Etoperidone
- Fluoxetine
- Mianserin
- Mirtazapine
- Nefazodone
- Nortriptyline
- Tedatioxetine
- Trazodone; Others: Adatanserin
- CEPC
- Cinanserin
- Cyproheptadine
- Deramciclane
- Dotarizine
- Eltoprazine
- Esmirtazapine
- FR-260,010
- Ketanserin
- Ketotifen
- Latrepirdine
- Metitepine/Methiothepin
- Methysergide
- Pizotifen
- Ritanserin
- RS-102,221
- S-14,671
- SB-200,646
- SB-206,553
- SB-221,284
- SB-228,357
- SB-242,084
- SB-243,213
- SDZ SER-082
- Xylamidine
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- 5-HT3
- 5-HT4
- 5-HT5
- 5-HT6
- 5-HT7 ligands
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5-HT3
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- Agonists: Piperazines: BZP
- Quipazine; Tryptamines: 2-Methyl-5-HT
- 5-CT; Others: Chlorophenylbiguanide
- Butanol
- Ethanol
- Halothane
- Isoflurane
- RS-56812
- SR-57,227
- SR-57,227-A
- Toluene
- Trichloroethane
- Trichloroethanol
- Trichloroethylene
- YM-31636
Antagonists: Antiemetics: AS-8112
- Alosetron
- Azasetron
- Batanopride
- Bemesetron
- Cilansetron
- Dazopride
- Dolasetron
- Galanolactone
- Granisetron
- Lerisetron
- Ondansetron
- Palonosetron
- Ramosetron
- Renzapride
- Tropisetron
- Zacopride
- Zatosetron; Atypical antipsychotics: Clozapine
- Olanzapine
- Quetiapine; Tetracyclic antidepressants: Amoxapine
- Mianserin
- Mirtazapine; Others: CSP-2503
- ICS-205,930
- MDL-72,222
- Memantine
- Nitrous Oxide
- Ricasetron
- Sevoflurane
- Tedatioxetine
- Thujone
- Tropanserin
- Vortioxetine
- Xenon
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5-HT4
|
- Agonists: Gastroprokinetic Agents: Cinitapride
- Cisapride
- Dazopride
- Metoclopramide
- Mosapride
- Prucalopride
- Renzapride
- Tegaserod
- Velusetrag
- Zacopride; Others: 5-MT
- BIMU8
- CJ-033,466
- PRX-03140
- RS-67333
- RS-67506
- SL65.0155
- Antagonists: GR-113,808
- GR-125,487
- L-Lysine
- Piboserod
- RS-39604
- RS-67532
- SB-203,186
- SB-204,070
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5-HT5A
|
- Agonists: Lysergamides: Ergotamine
- LSD; Tryptamines: 5-CT; Others: Valerenic Acid
Antagonists: Asenapine
- Latrepirdine
- Metitepine/Methiothepin
- Ritanserin
- SB-699,551
* Note that the 5-HT5B receptor is not functional in humans.
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5-HT6
|
- Agonists: Lysergamides: Dihydroergotamine
- Ergotamine
- Lisuride
- LSD
- Mesulergine
- Metergoline
- Methysergide; Tryptamines: 2-Methyl-5-HT
- 5-BT
- 5-CT
- 5-MT
- Bufotenin
- E-6801
- E-6837
- EMD-386,088
- EMDT
- LY-586,713
- N-Methyl-5-HT
- Tryptamine; Others: WAY-181,187
- WAY-208,466
Antagonists: Antidepressants: Amitriptyline
- Amoxapine
- Clomipramine
- Doxepin
- Mianserin
- Nortriptyline; Atypical antipsychotics: Aripiprazole
- Asenapine
- Clorotepine
- Clozapine
- Fluperlapine
- Iloperidone
- Olanzapine
- Tiospirone; Typical antipsychotics: Chlorpromazine
- Loxapine; Others: BGC20-760
- BVT-5182
- BVT-74316
- Cerlapirdine
- EGIS-12,233
- GW-742,457
- Ketanserin
- Latrepirdine
- Lu AE58054
- Metitepine/Methiothepin
- MS-245
- PRX-07034
- Ritanserin
- Ro04-6790
- Ro 63-0563
- SB-258,585
- SB-271,046
- SB-357,134
- SB-399,885
- SB-742,457
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5-HT7
|
- Agonists: Lysergamides: LSD; Tryptamines: 5-CT
- 5-MT
- Bufotenin; Others: 8-OH-DPAT
- AS-19
- Bifeprunox
- E-55888
- LP-12
- LP-44
- RU-24,969
- Sarizotan
Antagonists: Lysergamides: 2-Bromo-LSD
- Bromocriptine
- Dihydroergotamine
- Ergotamine
- Mesulergine
- Metergoline
- Methysergide; Antidepressants: Amitriptyline
- Amoxapine
- Clomipramine
- Imipramine
- Maprotiline
- Mianserin; Atypical antipsychotics: Amisulpride
- Aripiprazole
- Asenapine
- Clorotepine
- Clozapine
- Olanzapine
- Risperidone
- Sertindole
- Tiospirone
- Ziprasidone
- Zotepine; Typical antipsychotics: Chlorpromazine
- Loxapine; Others: Butaclamol
- EGIS-12,233
- Ketanserin
- LY-215,840
- Metitepine/Methiothepin
- Pimozide
- Ritanserin
- SB-258,719
- SB-258,741
- SB-269,970
- SB-656,104
- SB-656,104-A
- SB-691,673
- SLV-313
- SLV-314
- Spiperone
- SSR-181,507
- Vortioxetine
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Reuptake inhibitors
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SERT
|
- Selective serotonin reuptake inhibitors (SSRIs): Alaproclate
- Citalopram
- Dapoxetine
- Desmethylcitalopram
- Desmethylsertraline
- Escitalopram
- Femoxetine
- Fluoxetine
- Fluvoxamine
- Indalpine
- Ifoxetine
- Litoxetine
- Lubazodone
- Omiloxetine
- Panuramine
- Paroxetine
- Pirandamine
- RTI-353
- Seproxetine
- Sertraline
- Vilazodone
- Vortioxetine
- Zimelidine; Serotonin-norepinephrine reuptake inhibitors (SNRIs): Bicifadine
- Desvenlafaxine
- Duloxetine
- Eclanamine
- Levomilnacipran
- Milnacipran
- Sibutramine
- Venlafaxine; Serotonin-norepinephrine-dopamine reuptake inhibitors (SNDRIs): Brasofensine
- Diclofensine
- DOV-102,677
- DOV-21,947
- DOV-216,303
- NS-2359
- SEP-225289
- SEP-227,162
- Tedatioxetine
- Tesofensine; Tricyclic antidepressants (TCAs): Amitriptyline
- Butriptyline
- Cianopramine
- Clomipramine
- Desipramine
- Dosulepin
- Doxepin
- Imipramine
- Lofepramine
- Nortriptyline
- Pipofezine
- Protriptyline
- Trimipramine; Tetracyclic antidepressants (TeCAs): Amoxapine; Piperazines: Nefazodone
- Trazodone; Antihistamines: Brompheniramine
- Chlorphenamine
- Diphenhydramine
- Mepyramine/Pyrilamine
- Pheniramine
- Tripelennamine; Opioids: Pethidine
- Methadone
- Propoxyphene; Others: Cocaine
- CP-39,332
- Cyclobenzaprine
- Dextromethorphan
- Dextrorphan
- EXP-561
- Fezolamine
- Mesembrine
- Nefopam
- PIM-35
- Pridefine
- Roxindole
- SB-649,915
- Tofenacin
- Ziprasidone
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VMAT
|
- Ibogaine
- Reserpine
- Tetrabenazine
|
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Releasing agents
|
|
- Aminoindanes: 5-IAI
- AMMI
- ETAI
- MDAI
- MDMAI
- MMAI
- TAI; Aminotetralins: 6-CAT
- 8-OH-DPAT
- MDAT
- MDMAT; Oxazolines: 4-Methylaminorex
- Aminorex
- Clominorex
- Fluminorex; Phenethylamines (also Amphetamines, Cathinones, Phentermines, etc): 2-Methyl-MDA
- 4-CAB
- 4-FA
- 4-FMA
- 4-HA
- 4-MTA
- 5-APDB
- 5-Methyl-MDA
- 6-APDB
- 6-Methyl-MDA
- AEMMA
- Amiflamine
- BDB
- BOH
- Brephedrone
- Butylone
- Chlorphentermine
- Cloforex
- Amfepramone
- Metamfepramone
- DCA
- DFMDA
- DMA
- DMMA
- EBDB
- EDMA
- Ethylone
- Etolorex
- Fenfluramine (Dexfenfluramine, Levofenfluramine)
- Flephedrone
- IAP
- IMP
- Iofetamine
- Lophophine
- MBDB
- MDA
- MDEA
- MDHMA
- MDMA
- MDMPEA
- MDOH
- MDPEA
- Mephedrone
- Methedrone
- Methylone
- MMA
- MMDA
- MMDMA
- MMMA
- NAP
- Norfenfluramine
- 4-TFMA
- pBA
- pCA
- pIA
- PMA
- PMEA
- PMMA
- TAP; Piperazines: 2C-B-BZP
- 3-MeOPP
- BZP
- DCPP
- MBZP
- mCPP
- MDBZP
- MeOPP
- Mepiprazole
- pCPP
- pFPP
- pTFMPP
- TFMPP; Tryptamines: 4-Methyl-αET
- 4-Methyl-αMT
- 5-CT
- 5-MeO-αET
- 5-MeO-αMT
- 5-MT
- αET
- αMT
- DMT
- Tryptamine (itself); Others: Indeloxazine
- Tramadol
- Viqualine
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Enzyme inhibitors
|
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Anabolism
|
|
TPH
|
|
|
|
AAAD
|
- Benserazide
- Carbidopa
- Genistein
- Methyldopa
|
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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
- Befol
- Brofaromine
- Cimoxatone
- Clorgiline
- Esuprone
- Harmala alkaloids (Harmine
- Harmaline
- Tetrahydroharmine
- Harman
- Norharman, etc)
- Methylene Blue
- Metralindole
- Minaprine
- Moclobemide
- Pirlindole
- Sercloremine
- Tetrindole
- Toloxatone
- Tyrima
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Others
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Precursors
|
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Cofactors
|
- Ferrous iron (Fe2+)
- Magnesium (Mg2+)
- 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+)
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Others
|
- Activity enhancers: BPAP
- PPAP; Reuptake enhancers: Tianeptine
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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
|
|
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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
|
|
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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
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