Norquetiapine
(Synonyms: 11-(1-哌嗪基)二苯并[B,F][1,4]硫氮杂卓) 目录号 : GC49851
An active metabolite of quetiapine
Cas No.:5747-48-8
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Norquetiapine is an active metabolite of the atypical antipsychotic quetiapine .1 It is formed from quetiapine primarily by the cytochrome P450 (CYP) isoform CYP3A4. Norquetiapine selectively inhibits the norepinephrine transporter (NET; IC50 = 12 nM) over the serotonin (5-HT) and dopamine transporters (SERT and DAT; IC50s = 988 and >10,000 nM, respectively). It binds to the histamine H1 receptor (Ki = 3.5 nM), as well as the 5-HT receptor subtypes 5-HT1, 5-HT2, and 5-HT7 (Kis = 45-1,117 nM). It also binds to α1- and α2-adrenergic, dopamine D1-D5, and M1-M5 muscarinic receptors (Kis = 95-736, 196-1,419, and 23-453 nM, respectively). It acts as an antagonist at histamine H1, α1A- and α1D-adrenergic, as well as M1, M3, and M5 muscarinic receptors, in a concentration-dependent manner and as an agonist at the 5-HT1A receptor (EC50 = 4,898 nM). Norquetiapine (0.1, 0.5, and 1 mg/kg) reduces increases in immobility time in mice heterozygous for the gene encoding vesicular monoamine transporter 2 (Vmat2) but not in wild-type mice.
1.Jensen, N.H., Rodriguiz, R.M., Caron, M.G., et al.N-desalkylquetiapine, a potent norepinephrine reuptake inhibitor and partial 5-HT1A agonist, as a putative mediator of quetiapine’s antidepressant activityNeuropsychopharmacology33(10)2303-2312(2008)
| Cas No. | 5747-48-8 | SDF | Download SDF |
| 别名 | 11-(1-哌嗪基)二苯并[B,F][1,4]硫氮杂卓 | ||
| Canonical SMILES | C1(N=C(N2CCNCC2)C3=C(C=CC=C3)S4)=C4C=CC=C1 | ||
| 分子式 | C17H17N3S | 分子量 | 295.4 |
| 溶解度 | DMF: 16 mg/mL,DMSO: 3 mg/mL,Ethanol: 5 mg/mL,PBS (pH 7.2): 0.25 mg/mL | 储存条件 | -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
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1 mg | 5 mg | 10 mg |
| 1 mM | 3.3852 mL | 16.9262 mL | 33.8524 mL |
| 5 mM | 0.677 mL | 3.3852 mL | 6.7705 mL |
| 10 mM | 0.3385 mL | 1.6926 mL | 3.3852 mL |
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| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
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| % DMSO % % Tween 80 % saline | ||||||||||
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工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
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1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
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Norquetiapine blocks the human cardiac sodium channel Nav1.5 in a state-dependent manner
Eur J Pharmacol 2020 Oct 15;885:173532.PMID:32882214DOI:10.1016/j.ejphar.2020.173532.
Quetiapine, an atypical antipsychotic drug, is used for the treatment of schizophrenia and acute mania. Although a previous report showed that quetiapine blocked hERG potassium current, quetiapine has been considered relatively safe in terms of cardiovascular side effects. In the present study, we used the whole-cell patch-clamp technique to investigate the effect that quetiapine and its major metabolite Norquetiapine can exert on human cardiac sodium channels (hNav1.5). The half-maximal inhibitory concentrations of quetiapine and Norquetiapine at a holding potential of -90 mV near the resting potential of cardiomyocytes were 30 and 6 μM, respectively. Norquetiapine as well as quetiapine was preferentially bound in the inactivated state of the hNav1.5 channel. Norquetiapine slowed the recovery from inactivation of hNav1.5 and consequently induced strong use-dependent inhibition. Our results indicate that Norquetiapine blocks hNav1.5 current in concentration-, state- and use-dependent manners, suggesting that the blockade of hNav1.5 current by Norquetiapine may shorten the cardiac action potential duration and reduce the risk of QT interval prolongation induced by the inhibition of hERG potassium currents.
Active metabolites as antidepressant drugs: the role of Norquetiapine in the mechanism of action of quetiapine in the treatment of mood disorders
Front Psychiatry 2013 Sep 12;4:102.PMID:24062697DOI:10.3389/fpsyt.2013.00102.
Active metabolites of some antipsychotic drugs exhibit pharmacodynamic and pharmacokinetic properties that may be similar to or differ from the original compound and that can be translated by a different profile of responses and interactions to clinical level. Some of these antipsychotics' active metabolites might participate in mechanisms of antidepressant activity, as m-chlorophenylpiperazine (aripiprazole), 9-OH-risperidone and Norquetiapine. Norquetiapine exhibits distinct pharmacological activity from quetiapine and plays a fundamental role in its antidepressant efficacy. In this review, we analyze the differential pharmacological aspects between quetiapine and Norquetiapine, both from the pharmacokinetic and pharmacodynamic perspectives (affinity for dopaminergic, noradrenegic, and/or serotonergic receptors, etc.), as well as differential neuroprotective role. The pharmacological differences between the two drugs could explain the differential clinical effect, as well as some differences in tolerability profile and drug interactions. The available data are sufficient to arrive at the conclusion that antidepressant activity of quetiapine is mediated, at least in part, by the active metabolite Norquetiapine, which selectively inhibits noradrenaline reuptake, is a partial 5-HT1A receptor agonist, and acts as an antagonist at presynaptic α2, 5-HT2C, and 5-HT7 receptors.
Effects of Norquetiapine, the active metabolite of quetiapine, on cloned hERG potassium channels
Neurosci Lett 2018 Jan 18;664:66-73.PMID:29133173DOI:10.1016/j.neulet.2017.11.029.
Quetiapine is an atypical antipsychotic drug that is widely used for the treatment of schizophrenia. It is mainly metabolized by a cytochrome P450 system in the liver. Norquetiapine is a major active metabolite in humans with a pharmacological profile that differs distinctly from that of quetiapine. We used the whole-cell patch-clamp technique to investigate the effects of Norquetiapine on hERG channels that are stably expressed in HEK cells. Quetiapine and Norquetiapine inhibited the hERG tail currents at -50mV in a concentration-dependent manner with IC50 values of 8.3 and 10.8μM, respectively, which suggested equal potency. The block of hERG currents by Norquetiapine was voltage-dependent with a steep increase over a range of voltages for channel activation. However, at more depolarized potentials where the channels were fully activated, the block by Norquetiapine was voltage-independent. The steady-state inactivation curve of the hERG currents was shifted to the hyperpolarizing direction in the presence of Norquetiapine. Norquetiapine did not produce a use-dependent block. A fast application of Norquetiapine inhibited the hERG current elicited by a 5s depolarizing pulse to +60mV, which fully inactivated the hERG currents, suggesting an inactivated-state block. During a repolarizing pulse wherein the hERG current was slowly deactivated, albeit remaining in an open state, a fast application of Norquetiapine rapidly and reversibly inhibited the open state of the hERG current. Our results indicated that quetiapine and Norquetiapine had equal potency in inhibiting hERG tail currents. Norquetiapine inhibited the hERG current by preferentially interacting with the open and/or inactivated states of the channels.
Delirium Induced by Quetiapine and the Potential Role of Norquetiapine
Front Neurosci 2019 Aug 20;13:886.PMID:31481872DOI:10.3389/fnins.2019.00886.
Quetiapine in an atypical antipsychotic drug that is frequently used for delirium and behavioral and psychological symptoms in dementia. However, its potential anticholinergic effects, mediated primarily through its metabolite Norquetiapine, could present as counterproductive adverse effects in these situations. There is little data published discussing this potential negative impact on quetiapine's safety and tolerability, especially in the elderly. Here, we present what is, to our knowledge, the first published case report of delirium apparently induced by low-dose quetiapine, in a 95-year-old patient with no prior history of mental illness, and the potential role of its metabolite Norquetiapine.
β2 and α2 adrenergic receptors mediate the proneurogenic in vitro effects of Norquetiapine
Neural Regen Res 2021 Oct;16(10):2041-2047.PMID:33642392DOI:10.4103/1673-5374.308097.
Positive modulation of adult hippocampal neurogenesis may contribute to the therapeutic effects of clinically relevant antidepressant drugs, including atypical antipsychotics. Quetiapine, an antipsychotic which represents a therapeutic option in patients who are resistant to classical antidepressants, promotes adult hippocampal neurogenesis in preclinical studies. Norquetiapine, the key active metabolite of quetiapine in humans, has a distinctive receptor profile than the parent compound. The drug is indeed a high affinity norepinephrine transporter inhibitor and such activity has been proposed to contribute to its antidepressant effect. At present, no information is available on the effects of Norquetiapine on adult neurogenesis. We extensively investigated the activity of quetiapine and Norquetiapine on adult murine neural stem/progenitor cells and their progeny. Additionally, selective antagonists for β2/α2 adrenergic receptors allowed us to evaluate if these receptors could mediate quetiapine and Norquetiapine effects. We demonstrated that both drugs elicit in vitro proneurogenic effects but also that Norquetiapine had distinctive properties which may depend on its ability to inhibit norepinephrine transporter and involve β2/α2 adrenergic receptors. Animal care and experimental procedures were approved by the Institutional Animal Care and Use Committees (IACUC) at University of Piemonte Orientale, Italy (approval No. 1033/2015PR) on September 29, 2015.