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strong antihistamine activity might mean it could be regarded as more similar to sedating antihistamines in this context while these issues have not been regarded as sufficient cause for placing quetiapine under increased legal controls prescribers have been urged to show caution when prescribing quetiapine to individuals with characteristics that might place them at increased risk for drug misuse 60 61 62 63 64 overdose edit most 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 65 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 66 67 pharmacology edit pharmacodynamics edit see also atypical antipsychotic pharmacodynamics and antipsychotic comparison of medications quetiapine and metabolite 68 69 site qtp nqtp action ref sert tooltip serotonin transporter 10 000 927 blocker 69 net tooltip norepinephrine transporter 10 000 58 blocker 69 dat tooltip dopamine transporter 10 000 10 000 nd 69 5 ht 1a 320 432 45 partial agonist 69 70 5 ht 1b 1 109 2 050 1 117 nd 69 70 5 ht 1d 10 000 249 nd 69 70 5 ht 1e 1 250 2 402 97 nd 69 70 5 ht 1f 2 240 nd nd 70 5 ht 2a 96 101 48 antagonist 69 70 5 ht 2b nd 14 antagonist 69 5 ht 2c 2 502 107 antagonist 69 5 ht 3 10 000 394 antagonist 69 5 ht 4 nd nd nd nd 5 ht 5a 3 120 768 nd 69 5 ht 6 1 865 503 antagonist 69 5 ht 7 307 76 antagonist 69 α 1a 22 144 antagonist 69 α 1b 39 95 antagonist 69 α 2a 2 230 3 630 237 antagonist 69 70 α 2b 90 747 378 antagonist 69 70 α 2c 28 7 350 736 antagonist 69 70 β 1 10 000 10 000 nd 69 70 β 2 10 000 10 000 nd 69 70 d 1 712 214 antagonist 69 d 2 245 196 antagonist 69 d 2l 700 nd antagonist 70 d 2s 390 nd antagonist 70 d 3 340 483 567 antagonist 69 70 d 4 1 202 1 297 antagonist 69 d 4 2 1 600 nd antagonist 70 d 5 1 738 1 419 antagonist 69 h 1 2 2 11 3 5 antagonist 69 h 2 10 000 298 antagonist 69 h 3 10 000 10 000 nd 69 h 4 10 000 1 660 nd 69 m 1 858 39 antagonist 69 m 2 1 339 453 nd 69 m 3 10 000 23 antagonist 69 m 4 542 110 nd 69 m 5 1 942 23 antagonist 69 σ 1 220 3 651 10 000 nd 69 70 σ 2 1 344 1 050 nd 69 nmda pcp 10 000 nd antagonist 69 vdcc tooltip voltage dependent calcium channel 10 000 nd nd 69 70 herg tooltip human ether à go go related gene nd 10 000 ic 50 tooltip half maximal inhibitory concentration nd 69 values are k i nm unless otherwise noted the smaller the value the more strongly the drug binds to the site all data are for human cloned proteins except σ 1 guinea pig σ 2 rat and vdcc rat 69 70 quetiapine has the following pharmacological actions 71 72 73 74 3 75 76 77 dopamine d 1 d 2 d 3 d 4 and d 5 receptor antagonist serotonin 5 ht 1a receptor partial agonist 5 ht 2a 5 ht 2b 5 ht 2c 5 ht 3 5 ht 6 and 5 ht 7 receptor antagonist and 5 ht 1b 5 ht 1d 5 ht 1e and 5 ht 1f receptor ligand α 1 and α 2 adrenergic receptor antagonist histamine h 1 receptor antagonist muscarinic acetylcholine receptor antagonist this means quetiapine is a dopamine serotonin and adrenergic antagonist and a potent antihistamine with some anticholinergic properties 78 quetiapine binds strongly to serotonin receptors the drug acts as a partial agonist at 5 ht 1a receptors and as an antagonist to all other serotonin receptors it has affinity for 79 serial pet scans evaluating the d 2 receptor occupancy of quetiapine have demonstrated that quetiapine very rapidly disassociates from the d 2 receptor 80 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 81 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 α 1 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 72 82 due to the drug s sedating h 1 activity it is often prescribed at low doses for insomnia while some feel that low doses of drugs with antihistamine effects like quetiapine and mirtazapine are safer than drugs associated with physical dependency or other risk factors concern has been raised by some professionals that off label prescribing has become too widespread due to underappreciated hazards 83 when treating schizophrenia antagonism of d 2 receptor by quetiapine in the mesolimbic pathway relieves positive symptoms and antagonism of the 5 ht 2a receptor in the frontal cortex of the brain may relieve negative symptoms and reduce severity of psychotic episodes 19 84 85 quetiapine has fewer extrapyramidal side effects and is less likely to cause hyperprolactinemia when compared to other drugs used to treat schizophrenia so is used as a first line treatment 86 87 since the noradrenaline transporter is responsible for most of the dopamine clearance in the prefrontal cortex norquetiapine blocks reuptake of dopamine too accumulating the dopamine in the synapse 88 pharmacokinetics edit peak levels of quetiapine occur 1 5 hours after a dose 89 the plasma protein binding of quetiapine is 83 89 the major active metabolite of quetiapine is norquetiapine n desalkylquetiapine 69 quetiapine has an elimination half life of 6 or 7 hours 89 6 8 its metabolite norquetiapine has a half life of 9 to 12 hours 6 8 quetiapine is excreted primarily via the kidneys 73 and in feces 20 after hepatic metabolism the remainder 1 is excreted as the drug in its unmetabolized form 84 89 skeletal formula of norquetiapine chemistry edit quetiapine is a tetracyclic compound and is closely related structurally to clozapine olanzapine loxapine and other tetracyclic antipsychotics synthesis edit the 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 90 history edit sustained release edit astrazeneca 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 91 92 in may 2007 the united states fda approved seroquel xr for acute treatment of schizophrenia 93 during its 2007 q2 earnings conference astrazeneca announced plans to launch seroquel xr in the united states in august 2007 94 however seroquel xr has become available in american pharmacies only after the fda approved seroquel xr for use as maintenance treatment for schizophrenia in addition to acute treatment of the illness on 16 november 2007 95 the company has not provided a reason for the delay of seroquel xr s launch health canada approved sale of seroquel xr on 27 september 2007 96 in october 2008 the fda approved seroquel xr for the treatment of bipolar disorder including its associated depression and manic episodes in december 2008 biovail announced that the fda had accepted the company s anda to market its own version of sustained release quetiapine 97 biovail s sustained release tablets will compete with astrazeneca s seroquel xr in december 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 98 society and culture edit regulatory status edit in 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 99 in 2009 quetiapine xr was approved as adjunctive treatment of major depressive disorder 100 quetiapine received its initial approval from the us fda for the treatment of schizophrenia in 1997 3 101 in 2004 it received its second indication for the treatment of mania associated bipolar disorder 102 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 103 lawsuits edit in april 2010 the united states department of justice fined astrazeneca 520 million for the company s aggressive marketing of seroquel for off label uses 99 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 99 multiple lawsuits have been filed in relation to quetiapine s side effects in particular diabetes 104 105 106 107 approximately 10 000 108 lawsuits 109 have been filed against astrazeneca alleging that quetiapine caused problems ranging from slurred speech and chronic insomnia to deaths controversy edit in 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 110 a group of university of minnesota bioethicists charged that the trial involved an alarming number of ethical violations 111 nurofen plus tampering case edit in august 2011 the united kingdom 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 tablets instead 112 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 113 the contamination was later traced to in store tampering by a customer 114 references edit prescription medicines registration of new generic medicines and biosimilar medicines 2017 therapeutic goods administration tga 21 june 2022 retrieved 30 march 2024 anvisa 31 march 2023 rdc nº 784 listas de substâncias entorpecentes psicotrópicas precursoras e outras sob controle especial collegiate board 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system internet cited 2013 sep 18 greenwood village co thomsen healthcare 2013 1 2 3 quetiapine fumarate tablet dailymed ascend laboratories llc october 2013 archived from the original on 2 december 2013 retrieved 26 november 2013 1 2 3 4 5 6 7 8 quetiapine fumarate the american society of health system pharmacists archived from the original on 29 august 2017 retrieved 26 march 2017 1 2 3 4 komossa k depping am gaudchau a kissling w leucht s december 2010 second generation antipsychotics for major depressive disorder and dysthymia the cochrane database of systematic reviews 2012 12 cd008121 doi 10 1002 14651858 cd008121 pub2 pmc 11994262 pmid 21154393 anderson sl vande griend jp march 2014 quetiapine for insomnia a review of the literature pdf american journal of health system pharmacy 71 5 394 402 doi 10 2146 ajhp130221 pmid 24534594 s2cid 207292819 archived from the original pdf on 19 february 2020 riedel m müller n strassnig m spellmann i severus e möller hj april 2007 quetiapine in the treatment of schizophrenia and related disorders neuropsychiatric disease and treatment 3 2 219 235 doi 10 2147 nedt 2007 3 2 219 pmc 2654633 pmid 19300555 british national formulary bnf 74 74 ed british medical association 2017 p 383 isbn 978 0 85711 298 9 the top 300 of 2023 clincalc com archived from the original on 12 august 2025 retrieved 13 august 2025 quetiapine drug usage statistics clincalc drugstats database clincalc com retrieved 13 august 2025 the selection and use of essential medicines 2023 web annex a world health organization model list of essential medicines 23rd list 2023 geneva world health organization 2023 hdl 10665 371090 who mhp hps eml 2023 02 quetiapine fumarate the american society of health system pharmacists archived from the original on 10 february 2011 retrieved 3 april 2011 1 2 dev v raniwalla j october 2000 quetiapine a review of its safety in the management of schizophrenia drug safety 23 4 295 307 doi 10 2165 00002018 200023040 00003 pmid 11051217 1 2 suttajit s srisurapanont m xia j suttajit s maneeton b maneeton n may 2013 quetiapine versus typical antipsychotic medications for schizophrenia the cochrane database of systematic reviews 2013 5 cd007815 doi 10 1002 14651858 cd007815 pub2 pmc 11931684 pmid 23728667 archived from the original on 21 april 2016 1 2 3 4 5 leucht s cipriani a spineli l mavridis d orey d richter f et al september 2013 comparative efficacy and tolerability of 15 antipsychotic drugs in schizophrenia a multiple treatments meta analysis lancet 382 9896 951 962 doi 10 1016 s0140 6736 13 60733 3 pmid 23810019 s2cid 32085212 1 2 srisurapanont m maneeton b maneeton n 2004 srisurapanont m ed quetiapine for schizophrenia the cochrane database of systematic reviews 2004 2 cd000967 doi 10 1002 14651858 cd000967 pub2 pmc 7032613 pmid 15106155 kane jm correll cu 2010 pharmacologic treatment of schizophrenia dialogues in clinical neuroscience 12 3 345 357 doi 10 31887 dcns 2010 12 3 jkane pmc 3085113 pmid 20954430 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