| 词条 | Quetiapine | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 释义 |
| Watchedfields = changed | verifiedrevid = 443404910 | drug_name = | type = | IUPAC_name = 2-(2-(4-Dibenzo[b,f][1,4]thiazepine-11-yl-1-piperazinyl)ethoxy)ethanol | image = Quetiapine.svg | width = 250px | alt = | caption = | image2 = Quetiapine-from-xtal-3D-balls.png | width2 = 225px | pronounce = {{IPAc-en|k|w|ᵻ|ˈ|t|aɪ|.|ə|p|iː|n}} {{respell|kwi|TY|ə-peen}} | tradename = Seroquel, Temprolide, others | Drugs.com = {{drugs.com|monograph|quetiapine-fumarate}} | MedlinePlus = a698019 | licence_EU = | licence_US = Quetiapine | pregnancy_AU = B3 | pregnancy_US = C | pregnancy_category = | legal_AU = S4 | legal_CA = Rx-only | legal_US = Rx-only | legal_UK = POM | legal_status = | routes_of_administration = By mouth | bioavailability = 100%[1] | metabolism = Liver via CYP3A4-catalysed sulfoxidation to its active metabolite norquetiapine (N-desalkylquetiapine)[1] | protein_bound = 83%[2] | elimination_half-life = 7 hours (parent compound); 9–12 hours (active metabolite, norquetiapine)[2][3] | excretion = Kidney (73%), faeces (20%)[4][2][3][5] | CAS_number_Ref = {{cascite|correct|??}} | CAS_number = 111974-69-7 | ATC_prefix = N05 | ATC_suffix = AH04 | PubChem = 5002 | IUPHAR_ligand = 50 | DrugBank_Ref = {{drugbankcite|correct|drugbank}} | DrugBank = DB01224 | ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} | ChemSpiderID = 4827 | UNII_Ref = {{fdacite|correct|FDA}} | UNII = BGL0JSY5SI | KEGG_Ref = {{keggcite|correct|kegg}} | KEGG = D08456 | ChEBI_Ref = {{ebicite|correct|EBI}} | ChEBI = 8707 | ChEMBL_Ref = {{ebicite|correct|EBI}} | ChEMBL = 716 | C = 21| H = 25| N = 3| O = 2| S = 1 | molecular_weight = 383.5099 g/mol | SMILES = N\\1=C(\\c3c(Sc2c/1cccc2)cccc3)N4CCN(CCOCCO)CC4 | StdInChI_Ref = {{stdinchicite|correct|chemspider}} | StdInChI = 1S/C21H25N3O2S/c25-14-16-26-15-13-23-9-11-24(12-10-23)21-17-5-1-3-7-19(17)27-20-8-4-2-6-18(20)22-21/h1-8,25H,9-16H2 | StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} | StdInChIKey = URKOMYMAXPYINW-UHFFFAOYSA-N | solubility = 3.29 }}Quetiapine, sold under the trade name Seroquel among others, is an atypical antipsychotic used for the treatment of schizophrenia, bipolar disorder, and major depressive disorder.[6][7] Although not recommended, it is also used as a sleep aid due to its sedating effect.[8] It is taken by mouth.[6] Common side effects include sleepiness, constipation, weight gain, and dry mouth.[6] Other side effects include low blood pressure with standing, seizures, a prolonged erection, high blood sugar, tardive dyskinesia, and neuroleptic malignant syndrome.[6] In older people with dementia, its use increases the risk of death.[6] Use in the third trimester of pregnancy may result in a movement disorder in the baby for some time after birth.[6] Quetiapine is believed to work by blocking a number of receptors including serotonin and dopamine.[6] Quetiapine was developed in 1985 and approved for medical use in the United States in 1997.[6][9] It is available as a generic medication.[21] In the United States, the wholesale cost is about {{USD}}12 per month as of 2017.[10] In the United Kingdom, a month's supply costs the NHS about £60 as of 2017.[11] In 2016, it was the 86th most prescribed medication in the United States, with more than 8 million prescriptions.[12] Medical usesQuetiapine is primarily used to treat schizophrenia or bipolar disorder.[13] Quitapine targets both positive and negative symptoms of schizophrenia.[14] SchizophreniaA 2013 Cochrane review compared quetiapine to typical antipsychotics:
In a 2013 comparison of 15 antipsychotics in effectiveness in treating schizophrenia, quetiapine demonstrated standard effectiveness. It was 13-16% more effective than ziprasidone, chlorpromazine, and asenapine and approximately as effective as haloperidol and aripiprazole.[29] There is tentative evidence of the benefit of quetiapine versus placebo in schizophrenia; however, definitive conclusions are not possible due to the high rate of attrition in trials (greater than 50%) and the lack of data on economic outcomes, social functioning, or quality of life.[16] It is debatable whether, as a class, typical or atypical antipsychotics are more effective.[17] Both have equal drop-out and symptom relapse rates when typicals are used at low to moderate dosages.[18] While quetiapine has lower rates of extrapyramidal side effects, there is greater sleepiness and rates of dry mouth.[16] A Cochrane review comparing quetiapine to other atypical antipsychotic agents tentatively concluded that it may be less efficacious than olanzapine and risperidone; produce fewer movement related side effects than paliperidone, aripiprazole, ziprasidone, risperidone and olanzapine; and produce weight gain similar to risperidone, clozapine and aripiprazole. They concluded that it produces suicide attempt, suicide; death; QTc prolongation, low blood pressure; tachycardia; sedation; gynaecomastia; galactorrhoea, menstrual irregularity and white blood cell count at a rate similar to first generation antipsychotics.[19] Bipolar disorderIn those with bipolar disorder, quetiapine is used to treat depressive episodes; acute manic episodes associated with bipolar I disorder (as either monotherapy or adjunct therapy to lithium; valproate or lamotrigine); and maintenance treatment of bipolar I disorder (as adjunct therapy to lithium or divalproex). Major depressive disorderQuetiapine is effective when used by itself[7] and when used along with other medications in major depressive disorder (MDD).[7][20] However, sedation is often an undesirable side effect.[7] In the United States,[3] the United Kingdom[40] and Australia (while not subsidised by the Australian Pharmaceutical Benefits Scheme for treatment of MDD), quetiapine is licensed for use as an add-on treatment in MDD.[21] Alzheimer's diseaseQuetiapine does not decrease agitation among people with Alzheimer's. Quetiapine worsens intellectual functioning in the elderly with dementia and therefore is not recommended.[22] OthersThe use of low doses of quetiapine for insomnia, while common, is not recommended; there is little evidence of benefit and concerns regarding adverse effects.[23][24] It is sometimes used off-label, often as an augmentation agent, to treat conditions such as Tourette syndrome,[25] musical hallucinations[26] and anxiety disorders.[27] Quetiapine and clozapine are the most widely used medications for the treatment of Parkinson's disease psychosis due to their very low extrapyramidal side-effect liability. Owing to the risks associated with clozapine (e.g. agranulocytosis, diabetes mellitus, etc.), clinicians often attempt treatment with quetiapine first, although the evidence to support quetiapine's use for this indication is significantly weaker than that of clozapine.[28][49] Adverse effectsSources for incidence lists:[4][3][29][21][30][31]
Both typical and atypical antipsychotics can cause tardive dyskinesia.[34] According to one study, rates are lower with the atypicals at 3.9% as opposed to the typicals at 5.5%.[34] Although quetiapine and clozapine are atypical antipsychotics, switching to these atypicals is an option to minimize symptoms of tardive dyskinesia caused by other atypicals.[35] Weight gain can be a problem for some, with quetiapine causing more weight gain than fluphenazine, haloperidol, loxapine, molindone, olanzapine, pimozide, risperidone, thioridazine, thiothixene, trifluoperazine, and ziprasidone, but less than chlorpromazine, clozapine, perphenazine, and sertindole.[36] Studies conducted on beagles have resulted in the formation of cataracts. While there are reports of cataracts occurring in humans, controlled studies including thousands of patients have not demonstrated a clear causal association between quetiapine therapy and this side-effect.{{Citation needed|reason=Reference needed to April 2006 results of CATIE study.|date=September 2011}} However, the Seroquel website[37] still recommends users have eye examinations every six months. As with some other anti-psychotics, quetiapine may lower the seizure threshold,[38] and should be taken with caution in combination with drugs such as bupropion. Discontinuation and withdrawalQuetiapine should be discontinued gradually, with careful consideration from the prescribing doctor, to avoid withdrawal symptoms or relapse. The British National Formulary recommends a gradual withdrawal when discontinuing anti-psychotic treatment to avoid acute withdrawal syndrome or rapid relapse.[39] Due to compensatory changes at dopamine, serotonin, adrenergic and histamine receptor sites in the central nervous system, withdrawal symptoms can occur during abrupt or over-rapid reduction in dosage. However, despite increasing demand for safe and effective antipsychotic withdrawal protocols or dose-reduction schedules, no specific guidelines with proven safety and efficacy are currently available. Withdrawal symptoms reported to occur after discontinuation of antipsychotics include nausea; emesis; lightheadedness; diaphoresis; dyskinesia; orthostatic hypotension; tachycardia; insomnia; nervousness; dizziness; headache; non-stop crying; and anxiety.[72][40] Some have argued that additional somatic and psychiatric symptoms associated with dopaminergic super-sensitivity, including dyskinesia and acute psychosis, are common features of withdrawal in individuals treated with neuroleptics.[41][42] The present evidence suggests that these symptoms affect a small number of susceptible individuals treated with quetiapine.[43] Pregnancy and lactationPlacental exposure is least for quetiapine compared to other atypical antipsychotics.[30] The evidence is insufficient to rule out any risk to the foetus but available data suggests it is unlikely to result in any major foetal malformations.[2][5][31] It is secreted in breast milk and hence quetiapine-treated mothers are advised not to breastfeed.[2][5][31] OverdoseMost instances of acute overdosage result in only sedation, hypotension and tachycardia, but cardiac arrhythmia, coma and death have occurred in adults. Serum or plasma quetiapine concentrations are usually in the 1–10 mg/L range in overdose survivors, while postmortem blood levels of 10–25 mg/L are generally observed in fatal cases.[44] Non-toxic levels in postmortem blood extend to around 0.8 mg/kg, but toxic levels in postmortem blood can begin at 0.35 mg/kg.[45][46] PharmacologyPharmacodynamics{{See also|Atypical antipsychotic#Pharmacodynamics|Antipsychotic#Comparison of medications}}
Quetiapine has the following pharmacological actions:[50][51][52][53][54][55][56][57]
This means quetiapine is a dopamine, serotonin, and adrenergic antagonist, and a potent antihistamine with some anticholinergic properties.[58] Quetiapine binds strongly to serotonin receptors; the drug acts as partial agonist at 5-HT1A receptors.[59] Serial PET scans evaluating the D2 receptor occupancy of quetiapine have demonstrated that quetiapine very rapidly disassociates from the D2 receptor.[60] Theoretically, this allows for normal physiological surges of dopamine to elicit normal effects in areas such as the nigrostriatal and tuberoinfundibular pathways, thus minimizing the risk of side-effects such as pseudo-parkinsonism as well as elevations in prolactin.[61] Some of the antagonized receptors (serotonin, norepinephrine) are actually autoreceptors whose blockade tends to increase the release of neurotransmitters. At very low doses, quetiapine acts primarily as a histamine receptor blocker (antihistamine) and α1-adrenergic blocker. When the dose is increased, quetiapine activates the adrenergic system and binds strongly to serotonin receptors and autoreceptors. At high doses, quetiapine starts blocking significant amounts of dopamine receptors.[62][63] Off-label prescriptions, e.g. for chronic insomnia, of low-dose quetiapine is not recommended due to the harmful side-effects.[64] When treating schizophrenia, antagonism of D2 receptor by quetiapine in the mesolimmbic pathway relives positive symptoms and antagonism of the 5HT2A receptor in the frontal cortex of the brain relieves negative symptoms. [65][66][67] Quetiapine has fewer extrapyramidal side effects and is less likely to cause hyperprolacinaemia when compared to other drugs used to treat schizophrenia, so is used as a first line treatment.[68][69] PharmacokineticsThe major active metabolite of quetiapine is norquetiapine (N-desalkylquetiapine).[48] Quetiapine has a half-life of 7 hours. It is excreted primarily via the kidneys (73%) and in faeces (20%) after hepatic metabolism, the remainder (1%) is excreted as the drug in its unmetabolised form.[70][71] ChemistryQuetiapine is a tetracyclic compound and is closely related structurally to clozapine, olanzapine, loxapine, and other tetracyclic antipsychotics. SynthesisThe synthesis of quetiapine begins with a dibenzothiazepinone. The lactam is first treated with phosphoryl chloride to produce a dibenzothiazepine. A nucleophilic substitution is used to introduce the sidechain.[72] HistorySustained-releaseAstraZeneca submitted a new drug application for a sustained-release version of quetiapine in the United States, Canada, and the European Union in the second half of 2006 for treatment of schizophrenia.[73][74] AstraZeneca was to retain the exclusive right to market sustained-release quetiapine until 2017. The sustained-release quetiapine is marketed mainly as Seroquel XR. Other marketing names are Seroquel Prolong, Seroquel Depot and Seroquel XL On May 18, 2007, AstraZeneca announced that the U.S. FDA approved Seroquel XR for acute treatment of schizophrenia.[75] During its 2007 Q2 earnings conference, AstraZeneca announced plans to launch Seroquel XR in the U.S. during August 2007.[76] However, Seroquel XR has become available in U.S. pharmacies only after the FDA approved Seroquel XR for use as maintenance treatment for schizophrenia, in addition to acute treatment of the illness, on November 16, 2007.[77] The company has not provided a reason for the delay of Seroquel XR's launch. Health Canada approved sale of Seroquel XR on September 27, 2007.[78]In early October 2008, the FDA approved Seroquel XR for the treatment of bipolar depression and bipolar mania. According to AstraZeneca, Seroquel XR is "the first medication approved by the FDA for the once-daily acute treatment of both depressive and manic episodes associated with bipolar." On July 31, 2008, Handa Pharmaceuticals, based in Fremont, California, announced that its abbreviated new drug application (“ANDA”) for quetiapine fumarate extended-release tablets, the generic version of AstraZeneca’s SEROQUEL XR, has been accepted by the FDA. On December 1, 2008, Biovail announced that the FDA had accepted the company's ANDA to market its own version of sustained-release quetiapine.[79] Biovail's sustained-release tablets will compete with AstraZeneca's Seroquel XR. On December 24, 2008, AstraZeneca notified shareholders that the FDA had asked for additional information on the company's application to expand the use of sustained-release quetiapine for treatment of depression.[80] Society and cultureRegulatory statusIn the United States, the Food and Drug Administration (FDA) has approved quetiapine for the treatment of schizophrenia and of acute manic episodes associated with bipolar disorder (bipolar mania) and for treatment of bipolar depression.[81] In 2009, quetiapine XR was approved as adjunctive treatment of major depressive disorder.[82] Quetiapine received its initial indication from U.S. FDA for treatment of schizophrenia in 1997.[83] In 2004, it received its second indication for the treatment of mania-associated bipolar disorder.[84] In 2007 and 2008, studies were conducted on quetiapine’s efficacy in treating generalized anxiety disorder and major depression. Patent protection for the product ended in 2012; however, in a number of regions, the long-acting version remained under patent until 2017.[85] CostIn the United States as of 2015, the branded extended-release 400 mg pills cost between {{USD}}9.68 and {{USD}}23.16 each.[86] In 2017, the short-acting version had a wholesale cost of about {{USD}}12 per month.[10] In the United Kingdom, a month's supply, as of 2017, costs the NHS approximately £107.45.[11] This is following an increase of 30 to 70 fold in 2017/2018.[87] LawsuitsIn April 2010, the U. S. Department of Justice fined Astra-Zeneca $520 million for the company's aggressive marketing of Seroquel for off-label uses.[81] According to the Department of Justice, "the company recruited doctors to serve as authors of articles that were ghostwritten by medical literature companies and about studies the doctors in question did not conduct. AstraZeneca then used those studies and articles as the basis for promotional messages about unapproved uses of Seroquel."[81] Multiple lawsuits have been filed in relation to quetiapine's side-effects, in particular, diabetes.[88][89][90][91] Approximately 10,000[92] lawsuits[93] have been filed against AstraZeneca, alleging that quetiapine caused problems ranging from slurred speech and chronic insomnia to deaths. ControversyIn 2004, a young man named Dan Markingson committed suicide in a controversial Seroquel clinical trial at the University of Minnesota while under an involuntary commitment order.[94] A group of University of Minnesota bioethicists charged that the trial involved an alarming number of ethical violations.[95] Nurofen Plus tampering caseIn August 2011, the UK's Medicines and Healthcare products Regulatory Agency (MHRA) issued a class-4 drug alert following reports that some batches of Nurofen plus contained Seroquel XL instead.[96] Following the issue of the Class-4 Drug Alert, Reckitt Benckiser (UK) Ltd received further reports of rogue blister strips in cartons of two additional batches of Nurofen Plus tablets. One of the new batches contained Seroquel XL 50 mg tablets and one contained the Pfizer product Neurontin 100 mg capsules. Following discussions with the MHRA's Defective Medicines Report Centre (DMRC), Reckitt Benckiser (UK) Ltd decided to recall all remaining unexpired stock of Nurofen Plus tablets in any pack size, leading to a Class-1 Drug Alert.[97] The contamination was later traced to in-store tampering by a customer.[98] References1. ^1 {{cite book|last1=Brunton|first1=L|last2=Chabner|first2=B|last3=Knollman|first3=B|title=Goodman and Gilman's The Pharmacological Basis of Therapeutics|edition=12th|publisher=McGraw Hill Professional|year=2010|isbn=978-0071624428|url=https://books.google.com/books?id=bVUfAQAAQBAJ}} 2. ^1 2 3 4 {{cite web|title=Quetiapine 25 mg film-coated tablets - Summary of Product Characteristics|date=January 2013|accessdate=20 October 2013|website=electronic Medicines Compendium|publisher=Sandoz|url=http://www.medicines.org.uk/emc/medicine/26575/SPC/Quetiapine+25+mg+film-coated+tablets/|deadurl=yes|archiveurl=https://web.archive.org/web/20131020062812/http://www.medicines.org.uk/emc/medicine/26575/SPC/Quetiapine+25+mg+film-coated+tablets/|archivedate=20 October 2013|df=dmy-all}} 3. ^1 2 3 Truven Health Analytics, Inc. DrugPoint System (Internet) [cited 2013 Sep 18]. Greenwood Village, CO: Thomsen Healthcare; 2013. 4. ^1 2 {{cite web|title=quetiapine (Rx) - Seroquel, Seroquel XR|url=http://reference.medscape.com/drug/seroquel-xr-quetiapine-342984#10|website=Medscape Reference|publisher=WebMD|accessdate=11 October 2013|deadurl=no|archiveurl=https://web.archive.org/web/20131020163700/http://reference.medscape.com/drug/seroquel-xr-quetiapine-342984#10|archivedate=20 October 2013|df=}} 5. ^1 2 {{cite web|title=QUETIAPINE FUMARATE tablet QUETIAPINE FUMARATE (quetiapine fumarate ) tablet [Ascend Laboratories, LLC]|website=DailyMed|publisher=Ascend Laboratories, LLC|date=October 2013|accessdate=26 November 2013|url=http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=3112a006-1c61-47f2-84f5-9a7670d09c9b|deadurl=no|archiveurl=https://web.archive.org/web/20131202224630/http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=3112a006-1c61-47f2-84f5-9a7670d09c9b|archivedate=2 December 2013|df=}} 6. ^1 2 3 4 5 6 7 {{cite web|title=Quetiapine Fumarate|url=https://www.drugs.com/monograph/quetiapine-fumarate.html|publisher=The American Society of Health-System Pharmacists|accessdate=26 March 2017|deadurl=no|archiveurl=https://web.archive.org/web/20170829153057/https://www.drugs.com/monograph/quetiapine-fumarate.html|archivedate=29 August 2017|df=}} 7. ^1 2 3 {{cite journal |vauthors=Komossa K, Depping AM, Gaudchau A, Kissling W, Leucht S | title = Second-generation antipsychotics for major depressive disorder and dysthymia | journal = The Cochrane Database of Systematic Reviews | issue = 12 | pages = CD008121 | date = Dec 8, 2010 | pmid = 21154393 | doi = 10.1002/14651858.CD008121.pub2 }} 8. ^{{cite journal |author1=James J. Gugger |author2=Manouchkathe Cassagnol |title=Low-dose quetiapine is not a benign sedative-hypnotic agent |journal=The American Journal on Addictions |volume=17 |issue=5 |pages=454–455 |year=2008 |pmid=18770092 |doi=10.1080/10550490802266185}} 9. ^{{cite journal|last1=Riedel|first1=M|last2=Müller|first2=N|last3=Strassnig|first3=M|last4=Spellmann|first4=I|last5=Severus|first5=E|last6=Möller|first6=HJ|title=Quetiapine in the treatment of schizophrenia and related disorders|journal=Neuropsychiatric Disease and Treatment|date=April 2007|volume=3|issue=2|pages=219–35|pmid=19300555|doi=10.2147/nedt.2007.3.2.219|pmc=2654633 }} 10. ^1 {{cite web|title=NADAC as of 2017-03-22|url=https://data.medicaid.gov/Drug-Pricing-and-Payment/NADAC-as-of-2017-03-22/9q7x-utx9|publisher=Centers for Medicare and Medicaid Services|accessdate=26 March 2017|deadurl=no|archiveurl=https://web.archive.org/web/20170326230852/https://data.medicaid.gov/Drug-Pricing-and-Payment/NADAC-as-of-2017-03-22/9q7x-utx9|archivedate=26 March 2017|df=}} 11. ^1 2 {{cite book|title=British national formulary : BNF 74|date=2017|publisher=British Medical Association|isbn=978-0857112989|page=383|edition=74}} 12. ^{{cite web |title=The Top 300 of 2019 |url=https://clincalc.com/DrugStats/Top300Drugs.aspx |website=clincalc.com |accessdate=22 December 2018}} 13. ^{{cite web|title=quetiapine-fumarate|url=https://www.drugs.com/monograph/quetiapine-fumarate.html|website=The American Society of Health-System Pharmacists|accessdate=3 April 2011|deadurl=no|archiveurl=https://web.archive.org/web/20110210181855/http://www.drugs.com/monograph/quetiapine-fumarate.html|archivedate=10 February 2011|df=}} 14. ^{{cite journal |last1=Dev |first1=Vikram |last2=Raniwalla |first2=Joher |title=Quetiapine |journal=Drug Safety |date=2000 |volume=23 |issue=4 |pages=295–307 |doi=10.2165/00002018-200023040-00003|pmid=11051217 }} 15. ^1 {{cite journal|last1=Suttajit|first1=S|last2=Srisurapanont|first2=M|first3=J|last3=Xia|title=Quetiapine versus typical antipsychotic medications for schizophrenia|journal=Cochrane Database of Systematic Reviews|date=2013|volume=5|issue=5|url=http://www.cochrane.org/CD007815/SCHIZ_quetiapine-versus-typical-antipsychotic-drugs-for-schizophrenia|pages=CD007815.pub2|doi=10.1002/14651858.CD007815.pub2|pmid=23728667|deadurl=no|archiveurl=https://web.archive.org/web/20160421052117/http://www.cochrane.org/CD007815/SCHIZ_quetiapine-versus-typical-antipsychotic-drugs-for-schizophrenia|archivedate=2016-04-21|df=}} 16. ^1 {{cite journal|last=Srisurapanont|first=M|author2=Maneeton, B|author3= Maneeton, N|title=Quetiapine for schizophrenia|journal=Cochrane Database of Systematic Reviews|year=2004|issue=2|pages=CD000967|pmid=15106155|doi=10.1002/14651858.CD000967.pub2|editor1-last=Srisurapanont|editor1-first=Manit}} 17. ^{{vcite journal |author=Kane JM, Correll CU |title=Pharmacologic treatment of schizophrenia |journal=Dialogues Clin Neurosci |volume=12|issue=3 |pages=345–57 |year=2010 |pmid=20954430 |pmc=3085113}} 18. ^{{vcite journal |author=Schultz SH, North SW, Shields CG |title=Schizophrenia: a review |journal=Am Fam Physician |volume=75 |issue=12 |pages=1821–9 |year=2007 |month=June|pmid=17619525}} 19. ^{{cite journal |vauthors=Asmal L, Flegar SJ, Wang J, Rummel-Kluge C, Komossa K, Leucht S |title=Quetiapine versus other atypical antipsychotics for schizophrenia |journal=Cochrane Database of Systematic Reviews |volume=11 |issue= 11|pages=CD006625 |year=2013 |pmid=24249315 |doi=10.1002/14651858.CD006625.pub3 |url=|pmc=4167871 }} 20. ^{{cite journal |vauthors=Spielmans GI, Berman MI, Linardatos E, Rosenlicht NZ, Perry A, Tsai AC | year = 2013| title = Adjunctive Atypical Antipsychotic Treatment for Major Depressive Disorder: A Meta-Analysis of Depression, Quality of Life, and Safety Outcomes | url = | journal = PLoS Med | volume = 10 | issue = 3| page = e1001403 | doi = 10.1371/journal.pmed.1001403 | pmid=23554581 | pmc=3595214}} 21. ^1 2 {{cite book | title = Australian Medicines Handbook | year = 2013 | publisher = The Australian Medicines Handbook Unit Trust | isbn = 978-0-9805790-9-3 | edition = 2013 | place = Adelaide | editor = Rossi, S | url = https://books.google.com/books?id=tn3-swEACAAJ }} 22. ^{{cite journal |vauthors=Ballard C, Margallo-Lana M, Juszczak E, Douglas S, Swann A, Thomas A, O'Brien J, Everratt A, Sadler S, Maddison C, Lee L, Bannister C, Elvish R, Jacoby R | title = Quetiapine and rivastigmine and cognitive decline in Alzheimer's disease: randomised double blind placebo controlled trial | journal = BMJ | volume = 330 | issue = 7496 | pages = 874 | year = 2005 | pmid = 15722369 | pmc = 556156 | doi = 10.1136/bmj.38369.459988.8F }} 23. ^{{cite journal |vauthors=Coe HV, Hong IS | title = Safety of low doses of quetiapine when used for insomnia | journal = The Annals of Pharmacotherapy | volume = 46 | issue = 5 | pages = 718–22 | date = May 2012 | pmid = 22510671 | doi = 10.1345/aph.1Q697 }} 24. ^{{cite journal |vauthors=Maglione M, Maher AR, Hu J, etal | title = Off-Label Use of Atypical Antipsychotics: An Update | date = September 2011 | pmid = 22132426 }} 25. ^{{cite journal |vauthors=Mukaddes NM, Abali O | title = Quetiapine Treatment of Children and Adolescents with Tourette's Disorder | journal = Journal of Child and Adolescent Psychopharmacology | volume = 13 | issue = 3 | pages = 295–9 | year = 2003 | pmid = 14642017 | pmc = | doi = 10.1089/104454603322572624 }} 26. ^Oliver Sacks "Musicophilia" Knopf NY 2007 P.67 27. ^{{cite journal | author = Becker PM | title = Treatment of sleep dysfunction and psychiatric disorders | journal = Current Treatment Options in Neurology | volume = 8 | issue = 5 | pages = 367–375 | year = 2006 | pmid = 16901376 | pmc = | doi = 10.1007/s11940-006-0026-6 }} 28. ^{{cite journal |vauthors=Shotbolt P, Samuel M, David A | title = Quetiapine in the treatment of psychosis in Parkinson's disease | journal = Therapeutic Advances in Neurological Disorders | volume = 3 | issue = 6 | pages = 339–350 | date = November 2010 | pmid = 21179595 | pmc = 3002640 | doi = 10.1177/1756285610389656 }} 29. ^1 2 {{cite book|title=British National Formulary (BNF) 65|year=2013|publisher=Pharmaceutical Press|location=London, UK|isbn=9780857110848|page=235|url=https://books.google.com/books?id=fZLvtHELVdMC}} 30. ^1 2 3 {{cite book|last1=Taylor|first1=D|last2=Carol|first2=P|last3=Shitij|first3=K|title=The Maudsley prescribing guidelines in psychiatry|year=2012|publisher=Wiley-Blackwell|location=West Sussex|isbn=9780470979693|url=https://books.google.com/books?id=KY_2Qk4LqVYC}} 31. ^1 2 {{cite web|title=PRODUCT INFORMATION STADA(TM) Quetiapine (quetiapine fumarate Tablets 25 mg, 100 mg, 200 mg, 300 mg)|url=https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2012-PI-03014-1|date=30 November 2012|accessdate=19 September 2013|website=TGA eBusiness Services|publisher=STADA Pharmaceuticals Australia Pty Limited|deadurl=no|archiveurl=https://web.archive.org/web/20170327075724/https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2012-PI-03014-1|archivedate=27 March 2017|df=}} 32. ^1 2 3 4 {{cite journal |vauthors=Leucht S, Cipriani A, Spineli L, Mavridis D, Orey D, Richter F, Samara M, Barbui C, Engel RR, Geddes JR, Kissling W, Stapf MP, Lässig B, Salanti G, Davis JM | title = Comparative efficacy and tolerability of 15 antipsychotic drugs in schizophrenia: a multiple-treatments meta-analysis | journal = The Lancet | volume = 382 | issue = 9896 | pages = 951–962 | date = September 2013 | pmid = 23810019 | doi = 10.1016/S0140-6736(13)60733-3 }} 33. ^{{cite journal|title=Efficacy of Low-dose Pramipexole Augmentation in the Treatment of Refractory Psychotic Depression Complicated with Tardive Dyskinesia A Case Report|journal=Bulletin of Clinical Psychopharmacology|language=Turkish|author1=Erkan, A|author2=Pirildar, S|author3=Acarer, A|author4=Akdeniz, F|doi=10.5455/bcp.20111029071711|volume=21|issue=4|pages=353–355|year=2011|url=http://www.psikofarmakoloji.org/pdf/21_4_8.pdf|deadurl=yes|archiveurl=https://web.archive.org/web/20120113020807/http://www.psikofarmakoloji.org/pdf/21_4_8.pdf|archivedate=2012-01-13|df=|access-date=2018-12-12}} 34. ^1 {{cite journal |vauthors=Correll CU, Schenk EM | title = Tardive dyskinesia and new antipsychotics | journal = Current Opinion in Psychiatry | volume = 21 | issue = 2 | pages = 151–6 | date = March 2008 | pmid = 18332662 | doi = 10.1097/YCO.0b013e3282f53132 }} 35. ^{{cite journal | vauthors=Aia PG, Revuelta GJ, Cloud LJ, Factor SA | title = Tardive Dyskinesia | journal = Current Treatment Options in Neurology | volume = 13 | issue = 3 | pages = 231–241 | year = 2011 | pmid = 21365202 | doi = 10.1007/s11940-011-0117-x }} 36. ^Antipsychotic-Induced Weight Gain: A Comprehensive Research Synthesis {{webarchive|url=https://web.archive.org/web/20120425233956/http://altcancerweb.com/bipolar/weight-gain/antipsychotic-induced-weight-gain-1999.pdf |date=2012-04-25 }} Am J Psychiatry 1999;156:1686-1696. 37. ^Seroquel website {{webarchive|url=https://web.archive.org/web/20070217194559/http://seroquel.com/ |date=2007-02-17 }} 38. ^Seroquel Prescribing Information 39. ^{{cite book |editor1-first=BMJ |editor1-last=Group |title=British National Formulary |edition=57 |date=March 2009 |publisher=Royal Pharmaceutical Society of Great Britain |location=United Kingdom |page=192 |chapter=4.2.1 |quote=Withdrawal of antipsychotic drugs after long-term therapy should always be gradual and closely monitored to avoid the risk of acute withdrawal syndromes or rapid relapse.}} 40. ^{{cite journal |vauthors=Michaelides C, Thakore-James M, Durso R | title = Reversible withdrawal dyskinesia associated with quetiapine | journal = Mov Disord | volume = 20 | issue = 6 | pages = 769–70 | date = Jun 2005 | pmid = 15747370 | doi = 10.1002/mds.20427 }} 41. ^{{Cite journal | last1 = Miller | first1 = R. | last2 = Chouinard | first2 = G. | title = Loss of striatal cholinergic neurons as a basis for tardive and L-dopa-induced dyskinesias, neuroleptic-induced supersensitivity psychosis and refractory schizophrenia | url = http://www.biologicalpsychiatryjournal.com/article/0006-3223(93)90044-E/abstract | journal = Biol Psychiatry | volume = 34 | issue = 10 | pages = 713–38 |date=Nov 1993 | pmid =7904833 | doi = 10.1016/0006-3223(93)90044-E }} 42. ^{{cite journal | author = Moncrieff J | title = Does antipsychotic withdrawal provoke psychosis? Review of the literature on rapid onset psychosis (supersensitivity psychosis) and withdrawal-related relapse | journal = Acta Psychiatr Scand | volume = 114 | issue = 1 | pages = 3–13 | date = Jul 2006 | pmid = 16774655 | doi = 10.1111/j.1600-0447.2006.00787.x }} 43. ^1 {{cite journal |vauthors=Kim DR, Staab JP | title = Quetiapine discontinuation syndrome | journal = Am J Psychiatry | volume = 162 | issue = 5 | page = 1020 | date = May 2005 | pmid = 15863814 | doi = 10.1176/appi.ajp.162.5.1020 }} 44. ^R. Baselt, Disposition of Toxic Drugs and Chemicals in Man, 8th edition, Biomedical Publications, Foster City, CA, 2008, pp. 1355–1357. 45. ^{{cite journal |vauthors=Skov L, Johansen SS, Linnet K | title = Postmortem Femoral Blood Reference Concentrations of Aripiprazole, Chlorprothixene, and Quetiapine | journal = Journal of Analytical Toxicology | volume = 39 | issue = 1 | pages = 41–44 | date = Jan 2015 | doi = 10.1093/jat/bku121 | pmid = 25342720 }} 46. ^{{cite journal |vauthors=Skov L, Johansen SS, Linnet K | title = Postmortem Quetiapine Reference concentrations in Brain and Blood | journal = Journal of Analytical Toxicology | volume = 39 | issue = 7 | pages = 557–561 | date = Jul 2015 | doi = 10.1093/jat/bkv072 | pmid = 26159868 }} 47. ^{{cite web | title = PDSP Ki Database | website = Psychoactive Drug Screening Program (PDSP) | author1 = Roth, BL | author2 = Driscol, J | publisher = University of North Carolina at Chapel Hill and the United States National Institute of Mental Health | accessdate = 14 August 2017 | url = https://pdsp.unc.edu/databases/pdsp.php?knowID=0&kiKey=&receptorDD=&receptor=&speciesDD=&species=&sourcesDD=&source=&hotLigandDD=&hotLigand=&testLigandDD=&testFreeRadio=testFreeRadio&testLigand=quetiapine&referenceDD=&reference=&KiGreater=&KiLess=&kiAllRadio=all&doQuery=Submit+Query}} 48. ^1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 {{cite journal | vauthors = Jensen NH, Rodriguiz RM, Caron MG, Wetsel WC, Rothman RB, Roth BL | title = N-desalkylquetiapine, a potent norepinephrine reuptake inhibitor and partial 5-HT1A agonist, as a putative mediator of quetiapine's antidepressant activity | journal = Neuropsychopharmacology | volume = 33 | issue = 10 | pages = 2303–12 | year = 2008 | pmid = 18059438 | doi = 10.1038/sj.npp.1301646 | url = }} 49. ^1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 {{cite journal | vauthors = Schotte A, Janssen PF, Gommeren W, Luyten WH, Van Gompel P, Lesage AS, De Loore K, Leysen JE | title = Risperidone compared with new and reference antipsychotic drugs: in vitro and in vivo receptor binding | journal = Psychopharmacology | volume = 124 | issue = 1–2 | pages = 57–73 | year = 1996 | pmid = 8935801 | doi = 10.1007/bf02245606| url = }} 50. ^{{Cite journal |author=AstraZeneca |id=276521 |title=Seroquel (quietapine fumarate) tablets |url=http://www1.astrazeneca-us.com/pi/Seroquel.pdf |deadurl=yes |archiveurl=https://web.archive.org/web/20080414031803/http://www1.astrazeneca-us.com/pi/Seroquel.pdf |archivedate=2008-04-14 |df= }} 51. ^{{cite journal |vauthors=Richelson E, Souder T | title = Binding of antipsychotic drugs to human brain receptors focus on newer generation compounds | journal = Life Sciences | volume = 68 | issue = 1 | pages = 29–39 | date = November 2000 | pmid = 11132243 | doi = 10.1016/S0024-3205(00)00911-5 }} 52. ^{{cite book | url = https://books.google.com/?id=BKwkonZwZD0C&pg=PA778#v=onepage&q= | title = Neuropsychopharmacology: the fifth ... - Google Books | accessdate = | isbn = 978-0-7817-2837-9 | author1 = Davis, Kenneth L | author2 = Neuropsychopharmacology, American College of | year = 2002 }} 53. ^{{cite web |url=https://www.drugs.com/pro/seroquel.html |title=Seroquel Official FDA information, side effects and uses |publisher=Drugs.com |accessdate=2012-07-09 |deadurl=no |archiveurl=https://web.archive.org/web/20120604005526/http://www.drugs.com/pro/seroquel.html |archivedate=2012-06-04 |df= }} 54. ^{{cite web |url=http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?id=41375#section-15.2 |title=SEROQUEL (quetiapine fumarate) tablet, extended release |author=AstraZeneca Pharmaceuticals LP |date=March 2011 |website=DailyMed |publisher=National Library of Medicine |at=Section 12.2: Pharmacodynamics |accessdate=2011-04-26}} 55. ^National Institute of Mental Health. PDSD Ki Database (Internet) [cited 2013 Sep 18]. Chapel Hill (NC): University of North Carolina. 1998-2013. Available from: {{cite web|url=http://pdsp.med.unc.edu/pdsp.php |title=Archived copy |accessdate=July 5, 2013 |deadurl=yes |archiveurl=https://web.archive.org/web/20131108013656/http://pdsp.med.unc.edu/pdsp.php |archivedate=November 8, 2013 }} 56. ^{{cite journal |title=N-Desalkylquetiapine, a Potent Norepinephrine Reuptake Inhibitor and Partial 5-HT1A Agonist, as a Putative Mediator of Quetiapine's Antidepressant Activity |df= | doi = 10.1038/sj.npp.1301646 |pmid=18059438 |volume=33 |issue=10 |year=2008 |author=Jensen NH, Rodriguiz RM, Caron MG, Wetsel WC, Rothman RB, Roth BL |journal=Neuropsychopharmacology |pages=2303–12}} 57. ^{{cite journal |title=Active Metabolites as Antidepressant Drugs: The Role of Norquetiapine in the Mechanism of Action of Quetiapine in the Treatment of Mood Disorders |doi=10.3389/fpsyt.2013.00102 |pmid=24062697 |pmc=3770982 |volume=4 |pages=102 |year=2013 |journal=Frontiers in Psychiatry |author=López-Muñoz Francisco}} 58. ^{{cite journal|last=Chew|first=ML|title=Anticholinergic activity of 107 medications commonly used by older adults|pmid=18510583|doi=10.1111/j.1532-5415.2008.01737.x|volume=56|issue=7|year=2008|journal=J Am Geriatr Soc|pages=1333–41}} 59. ^{{cite web|last=Guzman|first=F|title=Mechanism of action of quetiapine|url=http://psychopharmacologyinstitute.com/antipsychotics/quetiapine/mechanism-of-action/|publisher=Psychopharmacology Institute|accessdate=20 January 2013|deadurl=no|archiveurl=https://web.archive.org/web/20130811004624/http://psychopharmacologyinstitute.com/antipsychotics/quetiapine/mechanism-of-action/|archivedate=11 August 2013|df=}} 60. ^{{cite journal | author = Kapur S, Seeman P | title = Does fast dissociation from the dopamine d(2) receptor explain the action of atypical antipsychotics?:a new hypothesis | journal = American Journal of Psychiatry | volume = 158 | issue = 3 | pages = 360–369 | year = 2001 | pmid = 11229973 | doi = 10.1176/appi.ajp.158.3.360 | url = http://ajp.psychiatryonline.org/cgi/content/abstract/158/3/360 | last2 = Seeman | first2 = P }} 61. ^{{cite journal | author = Seeman P | title = Atypical antipsychotics: mechanism of action | journal = Can J Psychiatry | volume = 47 | issue = 1 | pages = 27–38 | year = 2002 | pmid = 11873706 | doi = 10.1177/070674370204700106 }} 62. ^{{cite journal |vauthors=Richelson E, Souder T | title = Binding of antipsychotic drugs to human brain receptors focus on newer generation compounds | journal = Life Sciences | volume = 68 | issue = 1 | pages = 29–39 | date = November 2000 | pmid = 11132243 | doi = 10.1016/S0024-3205(00)00911-5 }} 63. ^{{cite journal |vauthors=Gefvert O, Lundberg T, Wieselgren IM, Bergström M, Långström B, Wiesel F, Lindström L | title = D2 and 5HT2A receptor occupancy of different doses of quetiapine in schizophrenia: a PET study | journal = European Neuropsychopharmacology | volume = 11 | issue = 2 | pages = 105–110 | date = April 2001 | pmid = 11313155 | doi = 10.1016/S0924-977X(00)00133-4 }} 64. ^{{cite web|title=Drug Use Evaluation: Low Dose Quetiapine (Seroquel/Seroquel XR)|url=http://www.govexec.com/pdfs/013111bb1a.pdf|website=Government Executive Media Group|publisher=Oregon State|accessdate=20 January 2016|deadurl=no|archiveurl=https://web.archive.org/web/20160422184014/http://www.govexec.com/pdfs/013111bb1a.pdf|archivedate=22 April 2016|df=}} 65. ^{{cite web |title=Quetiapine |url=https://www.drugbank.ca/drugs/DB01224 |website=www.drugbank.ca |accessdate=23 January 2019}} 66. ^{{cite journal |last1=Dev |first1=Vikram |last2=Raniwalla |first2=Joher |title=Quetiapine |journal=Drug Safety |date=2000 |volume=23 |issue=4 |pages=295–307 |doi=10.2165/00002018-200023040-00003|pmid=11051217 }} 67. ^{{cite web |title=Seroquel |url=https://www.accessdata.fda.gov/drugsatfda_docs/label/2004/20639se1-017,016_seroquel_lbl.pdf |website=FDA |accessdate=23 January 2019}} 68. ^{{cite journal |last1=Nemeroff |first1=CB |last2=Kinkead |first2=B |last3=Goldstein |first3=J |title=Quetiapine: preclinical studies, pharmacokinetics, drug interactions, and dosing. |journal=The Journal of Clinical Psychiatry |date=2002 |volume=63 Suppl 13 |pages=5–11 |pmid=12562141 }} 69. ^{{cite journal |last1=Kasper |first1=Siegfried |last2=Müller-Spahn |first2=Franz |title=Review of quetiapine and its clinical applications in schizophrenia |journal=Expert Opinion on Pharmacotherapy |date=24 February 2005 |volume=1 |issue=4 |pages=783–801 |doi=10.1517/14656566.1.4.783 |pmid=11249516 }} 70. ^{{cite web |title=Quetiapine |url=https://www.drugbank.ca/drugs/DB01224 |website=www.drugbank.ca |accessdate=23 January 2019}} 71. ^{{cite web |title=Seroquel |url=https://www.accessdata.fda.gov/drugsatfda_docs/label/2004/20639se1-017,016_seroquel_lbl.pdf |website=FDA |accessdate=23 January 2019}} 72. ^Warawa, E. J.; Migler, B. M.; 1988, {{US Patent|4879288}}. 73. ^{{cite press release|publisher=AstraZeneca|url=http://www.astrazeneca.com/pressrelease/5256.aspx|title=AstraZeneca Submits an NDA For Sustained Release Formulation Seroquel XR. For the treatment of schizophrenia.|date=2006-07-18|accessdate=2007-01-01|deadurl=no|archiveurl=https://web.archive.org/web/20061105230337/http://www.astrazeneca.com/pressrelease/5256.aspx|archivedate=2006-11-05|df=}} 74. ^{{cite press release|publisher=AstraZeneca|url=http://www.astrazeneca.com/pressrelease/5275.aspx|title=AstraZeneca Submits EU and Canadian Regulatory Filings for Sustained Release Formulation SEROQUEL XR for the Treatment of Schizophrenia|date=2006-10-19|accessdate=2007-01-01|deadurl=no|archiveurl=https://web.archive.org/web/20061107132140/http://www.astrazeneca.com/pressrelease/5275.aspx|archivedate=2006-11-07|df=}} 75. ^{{cite press release|publisher=AstraZeneca|url=http://www.astrazeneca.com/pressrelease/5330.aspx|title=FDA Approves AstraZeneca’s Once-Daily SEROQUEL XR Extended-Release Tablets For The Treatment Of Schizophrenia|date=2007-05-18|accessdate=2007-08-02|deadurl=no|archiveurl=https://web.archive.org/web/20070928040539/http://www.astrazeneca.com/pressrelease/5330.aspx|archivedate=2007-09-28|df=}} 76. ^{{cite press release|publisher=AstraZeneca|url=http://www.astrazeneca.com/pressrelease/5341.aspx|title=Second Quarter and Half Year Results 2007|date=2007-07-26|accessdate=2007-08-02|deadurl=no|archiveurl=https://web.archive.org/web/20070824192553/http://www.astrazeneca.com/pressrelease/5341.aspx|archivedate=2007-08-24|df=}} 77. ^{{cite press release|publisher=AstraZeneca|url=http://www.astrazeneca.com/pressrelease/5360.aspx|title=Seroquel XR Receives Approval from FDA for Maintenance Treatment of Schizophrenia|date=2007-11-16|accessdate=2007-12-03|deadurl=no|archiveurl=https://web.archive.org/web/20071204160258/http://www.astrazeneca.com/pressrelease/5360.aspx|archivedate=2007-12-04|df=}} 78. ^Notice of Compliance Information - Seroquel XR{{dead link|date=July 2016 |bot=InternetArchiveBot |fix-attempted=yes }} September 27, 2007, retrieved December 3, 2007 79. ^{{cite press release|publisher=Biovail|url=http://www.biovail.com/english/Investor%20Relations/Latest%20News/default.asp?s=1&state=showrelease&releaseid=1230930|title=Biovail Announces Filing of ANDA for Quetiapine XR Tablets|date=2008-12-01|deadurl=yes|archiveurl=https://web.archive.org/web/20070809023828/http://www.biovail.com/english/investor%20relations/latest%20news/default.asp?s=1|archivedate=2007-08-09|df=}} 80. ^{{cite press release|publisher=AstraZeneca|url=http://www.astrazeneca.com/media/latest-press-releases/seroquel-MDD-FDA-response?itemId=4477598|title=AstraZeneca Receives FDA Complete Response Letter on Seroquel XR for Major Depressive Disorder|date=2008-12-24|accessdate=2008-12-28|deadurl=no|archiveurl=https://web.archive.org/web/20101026190741/http://www.astrazeneca.com/media/latest-press-releases/seroquel-MDD-FDA-response?itemId=4477598|archivedate=2010-10-26|df=}} 81. ^1 2 {{cite web | url = http://www.justice.gov/opa/pr/2010/April/10-civ-487.html | title = Pharmaceutical Giant AstraZeneca to Pay $520 Million for Off-label Drug Marketing | publisher = Justice news, US Department of Justice | accessdate = 2012-07-16 | deadurl = no | archiveurl = https://web.archive.org/web/20120713201923/http://www.justice.gov/opa/pr/2010/April/10-civ-487.html | archivedate = 2012-07-13 | df = }} 82. ^{{cite web|last=Guzman|first=F|title=Quetiapine Indications: FDA-Approved and Off-label Uses|url=http://psychopharmacologyinstitute.com/antipsychotics/quetiapine/quetiapine-indications/|publisher=Psychopharmacology Institute|accessdate=19 January 2013|deadurl=no|archiveurl=https://web.archive.org/web/20140122132819/http://psychopharmacologyinstitute.com/antipsychotics/quetiapine/quetiapine-indications/|archivedate=22 January 2014|df=}} 83. ^{{cite web|title=QUETIAPINE FUMARATE|website=Electronic Orange Book|publisher=Food and Drug Administration|date=April 2007|url=http://www.accessdata.fda.gov/scripts/cder/ob/docs/obdetail.cfm?Appl_No=020639&TABLE1=OB_Rx|accessdate=2007-05-24|deadurl=no|archiveurl=https://web.archive.org/web/20090105000412/http://www.accessdata.fda.gov/scripts/cder/ob/docs/obdetail.cfm?Appl_No=020639&TABLE1=OB_Rx|archivedate=2009-01-05|df=}} 84. ^{{cite press release| publisher=AstraZeneca| date=2004-01-13| title=AstraZeneca Receives FDA Approval for SEROQUEL in Bipolar Mania| url=http://www.prnewswire.co.uk/cgi/news/release?id=115109| deadurl=no| archiveurl=https://web.archive.org/web/20110608181218/http://www.prnewswire.co.uk/cgi/news/release?id=115109| archivedate=2011-06-08| df=}} 85. ^{{cite web|author1=AstraZeneca|title=Pioneering science, life-changing medicines|url=https://www.sec.gov/Archives/edgar/data/901832/000095010314001994/dp44853_ex1501.htm|website=www.sec.gov|accessdate=26 March 2017|date=2013|deadurl=no|archiveurl=https://web.archive.org/web/20160306213537/http://www.sec.gov/Archives/edgar/data/901832/000095010314001994/dp44853_ex1501.htm|archivedate=6 March 2016|df=}} 86. ^{{cite news|last1=Langreth|first1=Robert|title=Decoding Big Pharma’s Secret Drug Pricing Practices|url=https://www.bloomberg.com/graphics/2016-drug-prices/|accessdate=15 July 2016|publisher=Bloomberg|date=June 29, 2016|deadurl=no|archiveurl=https://web.archive.org/web/20160713133019/http://www.bloomberg.com/graphics/2016-drug-prices/|archivedate=13 July 2016|df=}} 87. ^{{cite news |title=NHS hit by seven-fold increase in bill for certain drugs |url=https://www.hsj.co.uk/finance-and-efficiency/nhs-hit-by-seven-fold-increase-in-bill-for-certain-drugs/7022614.article |accessdate=29 August 2018 |publisher=Health Service Journal |date=8 June 2018}} 88. ^{{Cite news| url=http://www.madisonrecord.com/news/198781-seroquel-suit-claims-so-much-is-poured-into-marketing-and-away-from-research| title=Seroquel suit claims 'so much' is poured into marketing and away from research| work=The Madison / St. Clair Record| author=Ann Knef| date=2007-08-02| deadurl=no| archiveurl=https://web.archive.org/web/20080821141631/http://www.madisonrecord.com/news/198781-seroquel-suit-claims-so-much-is-poured-into-marketing-and-away-from-research| archivedate=2008-08-21| df=}} 89. ^{{cite news| author=Phil Milford| date=2009-03-11| work=Bloomberg.com| publisher=Bloomberg L.P.| url=https://www.bloomberg.com/apps/news?pid=newsarchive&sid=ayzJsK2HlF6s| title=AstraZeneca May Link Seroquel, Diabetes, Doctor Says| deadurl=no| archiveurl=https://web.archive.org/web/20150924191537/http://www.bloomberg.com/apps/news?pid=newsarchive&sid=ayzJsK2HlF6s| archivedate=2015-09-24| df=}} 90. ^{{cite web |url=http://www.fiercepharma.com/story/astrazeneca-wins-bellwether-seroquel-case/2010-03-19 |title=AstraZeneca wins bellwether Seroquel case |publisher=FiercePharma |date=2010-03-19 |accessdate=2012-07-09 |deadurl=no |archiveurl=https://web.archive.org/web/20120314034519/http://www.fiercepharma.com/story/astrazeneca-wins-bellwether-seroquel-case/2010-03-19 |archivedate=2012-03-14 |df= }} 91. ^{{Cite news|url=http://www.thelocal.se/28260/20100809/|title=AstraZeneca pays out million dollar damages|work=The Local|date=2010-08-09|deadurl=no|archiveurl=https://web.archive.org/web/20100817204556/http://www.thelocal.se/28260/20100809/|archivedate=2010-08-17|df=}} 92. ^{{cite web |url=http://www.marinecorpstimes.com/news/2010/08/ap-veterans-affairs-investigation-into-seroquel-083010/ |title=Questions loom over drug for sleepless vets - Marine Corps News | News from Afghanistan & Iraq |publisher=Marine Corps Times |accessdate=2012-07-09 |deadurl=yes |archiveurl=https://web.archive.org/web/20130602184342/http://www.marinecorpstimes.com/news/2010/08/ap-veterans-affairs-investigation-into-seroquel-083010/ |archivedate=2013-06-02 |df= }} 93. ^{{cite web |author=DUFF WILSON Published: July 18, 2011 |url=https://www.nytimes.com/2011/07/19/health/19drug.html?_r=2 |title=Heart Warning Added to Label on Popular Antipsychotic Drug |publisher=NyTimes |date=2011-07-19 |accessdate=2012-07-09 |deadurl=no |archiveurl=https://web.archive.org/web/20120702172131/http://www.nytimes.com/2011/07/19/health/19drug.html?_r=2 |archivedate=July 2, 2012 |df= }} 94. ^{{cite news|last=Elliott|first=Carl|title=The Deadly Corruption of Clinical Trials|url=https://www.motherjones.com/environment/2010/09/dan-markingson-drug-trial-astrazeneca|accessdate=2 December 2012|newspaper=Mother Jones|date=September–October 2010|deadurl=no|archiveurl=https://web.archive.org/web/20121117015108/https://www.motherjones.com/environment/2010/09/dan-markingson-drug-trial-astrazeneca|archivedate=17 November 2012|df=}} 95. ^{{cite news|last=Couzin-Frankel|first=Jennifer|title=Minnesota bioethicists critique their university|url=http://news.sciencemag.org/scienceinsider/2010/12/minnesota-bioethicists-critique-.html|accessdate=2 December 2012|newspaper=Science|date=December 7, 2010|deadurl=yes|archiveurl=https://web.archive.org/web/20130221014413/http://news.sciencemag.org/scienceinsider/2010/12/minnesota-bioethicists-critique-.html|archivedate=21 February 2013|df=}} 96. ^{{cite web |url=http://www.mhra.gov.uk/NewsCentre/Pressreleases/CON126226 |title=Press releases |publisher=MHRA |accessdate=2012-07-09 |deadurl=yes |archiveurl=https://web.archive.org/web/20120319232125/http://www.mhra.gov.uk/NewsCentre/Pressreleases/CON126226 |archivedate=2012-03-19 |df= }} 97. ^{{cite web |url=http://www.mhra.gov.uk/Publications/Safetywarnings/DrugAlerts/CON126268 |title=Drug Alerts |publisher=MHRA |accessdate=2012-07-09 |deadurl=no |archiveurl=https://web.archive.org/web/20120319232133/http://www.mhra.gov.uk/Publications/Safetywarnings/DrugAlerts/CON126268 |archivedate=2012-03-19 |df= }} 98. ^{{cite web |url=https://www.bbc.co.uk/news/uk-england-london-18203634 |title=BBC News - Nurofen Plus tampering: Christopher McGuire jailed |publisher=Bbc.co.uk |date=2012-05-28 |accessdate=2012-07-09 |deadurl=no |archiveurl=https://web.archive.org/web/20120614124729/http://www.bbc.co.uk/news/uk-england-london-18203634 |archivedate=2012-06-14 |df= }} External links{{Commonscat}}
| title = Pharmacodynamics | titlestyle = background:#ccccff | list1 ={{Adrenergic receptor modulators}}{{Dopamine receptor modulators}}{{Histamine receptor modulators}}{{Monoamine reuptake inhibitors}}{{Muscarinic acetylcholine receptor modulators}}{{Serotonin receptor modulators}} }}{{Tricyclics}} 12 : Alpha blockers|Antidepressants|Atypical antipsychotics|Dibenzothiazepines|Ethers|H1 receptor antagonists|Hypnotics|Mood stabilizers|Piperazines|Primary alcohols|Sedatives|RTT |
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开放百科全书收录14589846条英语、德语、日语等多语种百科知识，基本涵盖了大多数领域的百科知识，是一部内容自由、开放的电子版国际百科全书。