Dopamine receptor; Histamine receptor; Adrenergic Receptor
Dopamine D2 receptor, Ki=32 nM (human recombinant D2 receptor) [1]
5-Hydroxytryptamine 2A (5-HT2A) receptor, Ki=12 nM (human recombinant 5-HT2A receptor) [1]
5-Hydroxytryptamine 1A (5-HT1A) receptor, Ki=98 nM (human recombinant 5-HT1A receptor) [1]
Histamine H1 receptor, Ki=7 nM (human recombinant H1 receptor) [1]
Adrenergic α1 receptor, Ki=27 nM (human recombinant α1 receptor) [1]

In vitro activity: Quetiapine exhibits binding characteristics at the dopamine-2 receptor that are similar to those of clozapine and shows affinity for a variety of neurotransmitter receptors, including adrenergic, histamine, serotonin, and dopamine receptors.[1] Quetiapine is a novel dibenzothiazepine atypical antipsychotic. Quetiapine shows affinity for various neurotransmitter receptors including serotonin, dopamine, histamine, and adrenergic receptors and has binding characteristics at the dopamine-2 receptor similar to those of clozapine.[1]

---

---

In cells expressing human recombinant D2 receptor, Quetiapine Fumarate (ICI 204636) exhibited partial agonistic activity with an EC50=45 nM, and the maximum agonistic effect was 62% of that of dopamine [1]
It showed antagonistic activity against 5-HT2A receptor, and could completely block 5-HT-induced elevation of cellular calcium signaling at 10 nM [1]
In in vitro culture of rat hippocampal slices, 1 μM Quetiapine Fumarate (ICI 204636) enhanced synaptic plasticity in the CA1 region of the hippocampus, and the amplitude of long-term potentiation (LTP) was increased by 35% compared to the control group [2]
In in vitro culture of mouse cortical neurons, 0.5 μM of the drug inhibited potassium chloride-induced glutamate release, with the release volume decreased by 41% compared to the model group, and simultaneously upregulated the expression of GABA transporter GAT-1 (increased by 28%) [3]
Its antagonistic activity against histamine H1 receptor could inhibit histamine-induced cell proliferation with an IC50=15 nM [1]

Quetiapine possesses a preclinical profile that points to antipsychotic action, along with a prolonged rise in prolactin and a decreased propensity to induce extrapyramidal symptoms (EPS). In the limbic but not the motor brain regions, guetiapine modifies the expression of c-fos and neurotensin neurotransmission. In several behavioral and biochemical tests, quetiapine also exhibits clozapine-like activity and may have neuroprotective qualities.[1] Chronic restraint stress (CRS) in rats causes hippocampal cell proliferation and BDNF expression, which quetiapine dose-dependently prevents from leading to schizophrenia and depression. In stressed rats, a combination of gentapine (5 mg/kg) and Venlafaxine (2.5 mg/kg) prevents the decrease of BDNF and increases the proliferation of hippocampal cells, while individual drugs have negligible or no effects.[2] Guetiapine selectively affects the brain's limbic and cortical regions, especially the dopaminergic neurotransmission in these areas. Putamenal DA D2r occupancy is induced by gentiapine at lower levels than those observed in typical APDs. Quetiapine does not spare occupancy of the substantia nigra DA D2r, but it does produce preferential occupancy of temporal cortical DA D2r, 46.9%. In rats exposed to chronic stress through restraint, guetiapine reduces the decline in brain-derived neurotrophic factor (BDNF) in the hippocampus. Guetiapine (10 mg/kg) reverses the suppression of hippocampus neurogenesis caused by stress, as shown by an increase in pCREB-positive and BrdU-labeled cells compared to non-stressed rats, but not as much as those treated with a vehicle.[3]

---

In patients with clinical schizophrenia, oral administration of Quetiapine Fumarate (ICI 204636) at 300-600 mg daily resulted in a 42% reduction in the Scale for the Assessment of Positive Symptoms (SAPS) score and a 35% reduction in the Scale for the Assessment of Negative Symptoms (SANS) score compared to baseline after 6 weeks of treatment [1]
In patients with bipolar mania, an oral dose of 400 mg daily could rapidly control manic symptoms, with a 58% reduction in the Young Mania Rating Scale (YMRS) score after 1 week of treatment and an effective rate of 76% [1]
In a rat chronic stress model, oral administration of 20 mg/kg of the drug daily for 21 days improved stress-induced cognitive impairment. In the Morris water maze test, the escape latency was shortened by 38% compared to the model group, and the residence time in the target quadrant was prolonged by 45% [2]
In a mouse anxiety model, intraperitoneal injection of 10 mg/kg Quetiapine Fumarate (ICI 204636) increased the residence time in the open arms of the elevated plus maze from 18% to 42%, and simultaneously reduced the serum corticosterone level (decreased by 32%) [3]
In rat in vivo experiments, the drug could cross the blood-brain barrier, and the drug concentration in the cerebral cortex was 1.8 times that of the concurrent plasma concentration [1]

In vitro binding studies [Br J Pharmacol. 2016 Jan;173(1):155-66.]
Binding assays were performed using membranes prepared by standard methods from cells stably expressing cloned human targets. Displacement binding was performed using either scintillation proximity assay (SPA) (NET/HEK293F cells and 5‐HT2C/CHO‐K1 cells) or filtration (5‐HT transporter [SERT]/HEK293 cells, dopamine transporter [DAT]/CHO‐S cells, D2S/CHO‐K1 cells, 5‐HT1A/CHO cells and 5‐HT2A/CHO cells) using tritiated radioligands (MeNER, mesulergine, MADAM [2‐(2‐dimethylaminomethyl‐phenylsulphanyl)‐5‐methyl‐phenylamine], WIN 35428, raclopride, WAY100635 and MDL100907 respectively). The majority of IC50 values were calculated with fitting model 205 in XLfit. 5‐HT2A and 5‐HT2C IC50 values were calculated using prism software by GraphPad. Mean apparent inhibition constant (K i) values were calculated using the Cheng–Prusoff equation from data derived from at least three independent experiments. In vitro assessment of affinity at glutamate receptors was performed on preparations of rat cerebral cortex tissue. Binding at NMDA receptors was evaluated with [3H]‐CGP39653 [3H]‐TCP and [3H]‐MDL 105,519 binding at kainite receptors was evaluated with [3H]‐kainic acid and binding at AMPA receptors was evaluated with [3H]‐AMPA according to standard validated protocols under conditions defined by the contractor. Compounds were evaluated in singlicate across eight concentrations (0.01, 0.1, 0.3, 1, 3, 10, 30 and 100 μM).

---

Receptor binding assay: Cell membrane preparations expressing human recombinant D2, 5-HT2A, 5-HT1A, H1, and α1 receptors were incubated with corresponding radiolabeled ligands respectively. Gradient concentrations of Quetiapine Fumarate (ICI 204636) were added to compete for binding sites. After incubation at 37°C for 90 minutes, bound and free ligands were separated. Binding affinity was quantified by radioactivity counting, and Ki values for each receptor were calculated [1]
5-HT2A receptor antagonistic activity assay: 5-HT2A receptor-expressing cells loaded with calcium fluorescent probes were pre-incubated with different concentrations of the drug for 30 minutes, then 5-HT was added to stimulate calcium influx. Changes in fluorescence intensity were detected to evaluate the blocking effect of the drug on the receptor [1]
D2 receptor agonistic activity assay: D2 receptor-expressing cells were co-incubated with the drug, and changes in intracellular cAMP concentration were detected. Compared with dopamine positive control, EC50 and maximum agonistic effect were calculated [1]

Cell Line: N9 microglial cells
Concentration: 0, 0.1, 1, 10, 50, and 100 μM
Incubation Time: 24 hours
Result: Had no significant effect on cell viabilities at various concentrations under 100 μM, in which significant toxicity could be observed.

---

In vitro functional studies [Br J Pharmacol. 2016 Jan;173(1):155-66.]
Uptake inhibition assays were performed using HEK293F cells stably expressing human NET, SERT and DAT. Cryopreserved cells were re‐suspended at 60K per well, centrifuged at 110 g for 1 min and incubated at 37°C for 3 h. Uptake inhibition was measured using the neurotransmitter transporter dye by a method slightly modified from that reported by Jorgensen et al. 2008. The most significant alteration to the method is that fluorescence intensity was evaluated on an Envision reader. Data were analysed by calculating the % effect with respect to total (0.5% DMSO final) and background signals. D2S pA2 was measured by the ability of a compound to inhibit the response to 3 μM dopamine (~EC80), using a GTPγS filtration binding assay similar to the method previously described by Lazareno (1999; Hudzik et al., 2008). 5‐HT1A agonist activity (potency and maximal concentration [Emax]) was determined with a GTPγS SPA binding assay using membranes derived from CHO cells stably expressing recombinant human 5‐HT1A receptors. Assay conditions are based on those previously reported (Jerning et al., 2002), though modified to an SPA format. An efficacy of 100% was defined as the maximal response to 5‐HT. 5‐HT2A and 5‐HT2C antagonist activity was measured with a FLIPR‐based method, as previously reported (Porter et al., 1999) using cell lines expressing 5‐HT2A and 5‐HT2C receptors.

---

Hippocampal slice LTP detection: Rat hippocampus was isolated to prepare 300 μm slices, which were equilibrated in artificial cerebrospinal fluid for 2 hours. After incubation with 0.1-5 μM Quetiapine Fumarate (ICI 204636) for 1 hour, LTP was induced in the CA1 region by electrical stimulation. The field excitatory postsynaptic potential (fEPSP) amplitude was recorded and monitored continuously for 2 hours [2]
Cortical neuron neurotransmitter release assay: Mouse cortical neurons were seeded in culture plates and cultured for 14 days. After incubation with 0.1-2 μM of the drug for 24 hours, neurotransmitter release was stimulated with potassium chloride. Cell supernatants were collected, and glutamate and GABA concentrations were detected by high-performance liquid chromatography [3]
GAT-1 protein expression detection: After the above neuron culture experiment, total cellular protein was extracted. GAT-1 protein level was detected by Western blot, with β-actin as internal reference to quantify changes in protein expression [3]

Absorption, Distribution and Excretion
Quetiapine is rapidly and well absorbed after oral administration. Steady-state plasma concentrations are reached within 48 hours, and peak plasma concentrations are reached within 1.5 hours. The bioavailability of the tablets is 100%. In Han Chinese patients with schizophrenia, after oral administration of a 300 mg extended-release formulation, the steady-state peak plasma concentration (Cmax) was approximately 467 ng/mL, and the steady-state AUC was 5094 ng·h/mL. Food affects the absorption of quetiapine, increasing Cmax by 25% and AUC by 15%. After oral administration of radiolabeled quetiapine, less than 1% of the original drug is detected in the urine, indicating active metabolism of quetiapine. Approximately 73% of the dose is detected in urine, and approximately 20% is detected in feces. Quetiapine is distributed throughout the body. The apparent volume of distribution is approximately 10 ± 4 L/kg. In a clinical study, the fasting clearance of quetiapine in healthy volunteers was 101.04 ± 39.11 L/h. Lower doses of quetiapine may be required in elderly patients, as clearance may be reduced by up to 50%. Lower doses may also be required in patients with hepatic impairment. Oral absorption of quetiapine fumarate is rapid, reaching peak plasma concentrations within 1.5 hours. The bioavailability of tablets is 100% compared to solutions. Food has minimal effect on the bioavailability of quetiapine, increasing Cmax and AUC by 25% and 15%, respectively. Steady-state plasma concentrations are expected to be reached within two days after administration. Quetiapine is widely distributed throughout the body, with an apparent volume of distribution of 10 ± 4 L/kg. At therapeutic concentrations, its plasma protein binding is 83%. The oral clearance of quetiapine in patients with hepatic impairment (n=8) was, on average, 30% lower than in healthy subjects. In 2 of the 8 patients with hepatic impairment, the AUC and Cmax values were 3 times higher than in healthy subjects. Because quetiapine is primarily metabolized by the liver, plasma drug concentrations are expected to be higher in individuals with impaired liver function…
For more complete data on absorption, distribution, and excretion of quetiapine (8 items), please visit the HSDB record page.

---

Metabolism/Metabolites
Quetiapine is primarily metabolized by the liver. Sulfonation and oxidation are the main metabolic pathways for this drug. In vitro studies have shown that cytochrome P450 3A4 metabolizes quetiapine to an inactive sulfonyl metabolite and participates in the metabolism of its active metabolite, N-desalkylquetiapine. CYP2D6 also participates in the metabolism of quetiapine. One study identified three metabolites of N-desalkylquetiapine. Two metabolites were identified as N-desalkylquetiapine sulfoxide and 7-hydroxy-N-desalkylquetiapine. CYP2D6 has been shown to be responsible for the metabolism of quetiapine to the pharmacologically active metabolite, 7-hydroxy-N-desalkylquetiapine. Individual variability in CYP2D6 metabolism may affect the concentration of the active metabolite. Quetiapine is primarily metabolized in the liver to inactive metabolites via sulfonation and oxidation. In vitro studies have shown that cytochrome P-450 (CYP) 3A4 isoenzymes are involved in the metabolism of quetiapine to inactive sulfoxide metabolites, which are the major metabolites. Based on in vitro studies, quetiapine and its nine metabolites appear unlikely to inhibit CYP isoenzymes 1A2, 3A4, 2C9, 2C19, or 2D6. Known metabolites of quetiapine include 7-hydroxyquetiapine and quetiapine sulfoxide. It is primarily metabolized in the liver. Its main metabolic pathway involves cytochrome P450 3A4 (CYP3A4)-mediated sulfonation and the oxidation of terminal alcohols to carboxylic acids. The major sulfoxide metabolite of quetiapine is inactive. Quetiapine also undergoes hydroxylation, O-dealkylation, N-dealkylation, and II-binding reactions of the dibenzothiazole ring. 7-Hydroxy and 7-hydroxy-N-dealkylated metabolites appear to be active, but at extremely low concentrations. Elimination pathway: Quetiapine is primarily eliminated via hepatic metabolism. Following a single oral dose of 14C-quetiapine, less than 1% of the administered dose is excreted unchanged, indicating rapid metabolism. Approximately 73% and 20% of the dose are recovered in urine and feces, respectively. Half-life: 6 hours. The mean terminal half-life of quetiapine is approximately 6–7 hours.

---

After oral administration of 100 mg quetiapine fumarate (ICI 204636) to humans, the time to peak concentration (Tmax) is 1.5 hours and the peak plasma concentration (Cmax) is 0.7 μg/mL [1]
The oral bioavailability is approximately 83%, absorption is not affected by food, and the plasma protein binding rate is 83% [1]
It is mainly metabolized by hepatic CYP3A4 to generate the active metabolite N-desalkylquetiapine. The half-life (t1/2) is 12 hours, and the elimination half-life (t1/2) of the parent drug is 6.8 hours [1]
The plasma clearance rate is 11 mL/min/kg, the volume of distribution (Vd) is 10 L/kg, and it can be widely distributed throughout the body tissues, with a high concentration in the central nervous system [1]
Within 24 hours after administration, approximately 73% of the metabolites are excreted in the urine and 21% in the feces [1]

Effects During Pregnancy and Lactation
◉ Overview of Use During Lactation
When a mother takes up to 400 mg of quetiapine daily, the concentration of the drug in her breast milk is less than 1% of the mother's weight-adjusted dose. Limited long-term follow-up of infants exposed to quetiapine indicates that the infants generally develop normally. A safety rating system considers quetiapine suitable for use during lactation. A systematic review of second-generation antipsychotics concluded that quetiapine appears to be a first- or second-line drug during lactation. Infant somnolence and developmental milestones should be monitored, especially when other antipsychotics are used concurrently. Rare case reports of galactorrhea and spitting up milk have been reported. ◉ Effects on Breastfed Infants
One mother took 25 mg of quetiapine orally daily during pregnancy and continued to take 50 mg of quetiapine orally daily during lactation. The infant was well at 6 weeks of age. No further follow-up was reported.
Another infant whose mother took 200 mg of quetiapine daily was exclusively breastfed at 8 weeks of age. The infant developed well at 4.5 months of age, and no adverse reactions were reported. A breastfeeding mother with postpartum psychosis began taking quetiapine at 25 mg daily 6 weeks postpartum, concurrently with an unspecified benzodiazepine. Over the next 6 weeks, the quetiapine dose was gradually increased to 200 mg daily, and then to 300 mg daily over the following 4 weeks (16 weeks postpartum). Mirtazapine 15 mg/day was started at 8 weeks postpartum. Breastfeeding (level not specified) continued until 16 weeks postpartum, when it was discontinued due to decreased milk production. During this period, the infant experienced excessive sleepiness until the benzodiazepine dose was reduced and the quetiapine dose was increased. The infant was followed up for at least 2 months after breastfeeding was discontinued, and no effects on the infant's growth, motor, or psychological development were observed, nor were any withdrawal symptoms observed.
A breastfeeding mother with bipolar disorder started taking paroxetine 20 mg four months postpartum, followed by quetiapine 200 mg twice daily six months postpartum. She breastfed regularly (feeding extent not specified), and the infant experienced no significant adverse reactions.
A woman who had been taking quetiapine 400 mg and fluvoxamine 200 mg long-term throughout her pregnancy and postpartum period took these medications. She partially breastfed her infant for three months from birth (feeding extent not specified). No adverse reactions were observed, and the infant developed normally.
Six breastfeeding mothers taking antidepressants (usually paroxetine) for postpartum major depressive disorder also took quetiapine at doses ranging from 25 to 400 mg daily. Their breastfed infants underwent developmental assessments using the Bayley Infant Development Scales at 9 to 18 months of age. One infant scored slightly lower on the psychomotor development scale, and another scored slightly lower on the psychomotor development scale. All other scores were within the normal range. The authors concluded that the low scores of these two infants were likely not caused by medication in their breast milk. One mother gave birth to an infant while taking 400 mg of quetiapine, 40 mg of fluoxetine, and 20 mg of oxycodone three times daily. The infant was breastfed 6-7 times daily and received 120 mcg of morphine three times daily due to opioid withdrawal symptoms. At 3 months of age, the infant's weight was found to be in the 25th percentile for its age, compared to the 50th percentile at birth. The authors attributed the weight loss to opioid withdrawal. The infant's Denver Developmental Score was consistent with its chronological age. A 60-week-old infant, 50% breastfed, continued breastfeeding while the mother was receiving 75 mg of quetiapine and 225 mg of venlafaxine daily. No adverse reactions were reported in the mother's or medical records.
A woman with bipolar disorder started taking a therapeutic dose of sodium valproate after giving birth to twins. Twenty days postpartum, she began taking quetiapine 200 mg and olanzapine 15 mg, taken daily at 11 PM. She stopped breastfeeding at night and discarded expressed milk at 7 AM. She then breastfed until 11 PM. This mother continued breastfeeding according to this schedule for 15 months. Monthly follow-ups of the infants showed normal growth and development, and no adverse reactions were observed in the infants by the pediatrician or parents.
A mother took 100 mg of quetiapine nightly to treat bipolar disorder and breastfed two premature infants. At the last follow-up (specific date not specified), both infants were reported to be developing normally.
A woman with bipolar disorder took 25 mg of quetiapine and 100 mg of lamotrigine daily during both pregnancies to treat bipolar disorder. She did not breastfeed after the first delivery but breastfed her second infant (feeding extent not specified). At a 2-month health check, the infant's developmental milestones were all met. One woman with postpartum bipolar II depression was taking 300 mg lamotrigine and 300 mg quetiapine daily. The authors reported no major adverse events in her breastfed infant (exposure to feeding). One author reported a case of an infant who was breastfed (exposure to feeding) while the mother was receiving treatment for bipolar disorder postpartum. The mother was taking 200 mg quetiapine daily. The mother reported no adverse events in the infant. A prospective cohort study conducted in a maternal and infant psychiatric ward in India followed two infants exposed to quetiapine through breast milk; most infants received partial supplemental therapy. Neither infant experienced any short-term adverse events. The infants were followed up for 1 to 3 months after discharge; one infant exposed to quetiapine in utero developed motor and intellectual developmental delays. A woman took 300 mg of extended-release quetiapine orally daily during the last trimester of pregnancy and postpartum. Three months postpartum, her breastfed infant (feeding extent not specified) showed no significant adverse reactions and developed normally. Patients taking second-generation antipsychotics while breastfeeding (n = 576) registered in the National Atypical Antipsychotic Pregnancy Registry were compared with a control group of breastfeeding patients not taking second-generation antipsychotics (n = 818). Among patients taking second-generation antipsychotics, 60.4% were concurrently taking two or more psychotropic medications. A review of pediatric medical records showed no adverse reactions in infants, regardless of whether they received monotherapy or combination therapy with second-generation antipsychotics. No cases of women taking quetiapine were reported. Effects on lactation and breast milk: Unlike phenothiazines, quetiapine has minimal effect on serum prolactin levels. However, there have been reports of galactorrhea. For mothers who have established lactation, their prolactin levels may not affect their ability to breastfeed. One non-breastfeeding woman experienced galactorrhea while taking venlafaxine 112.5 mg/day and quetiapine. The woman experienced galactorrhea after a few days of starting quetiapine at 12.5 mg/day, which was increased to 50 mg/day. She had been taking galactorrhea for 10 days. Her serum prolactin level was 27.3 mcg/L (normal range 2 to 30 mcg/L), which decreased to 8.5 mcg/L two weeks after discontinuation. The galactorrhea stopped after one week.
Patients taking second-generation antipsychotics while breastfeeding (n = 576) registered with the National Registry of Atypical Antipsychotics for Pregnancy were compared with a control group of breastfeeding patients (n = 818) with a primary diagnosis of major depressive disorder and anxiety disorder, who typically received SSRIs or SNRIs but did not use second-generation antipsychotics. Among the women taking second-generation antipsychotics, 60.4% were also taking more than one psychotropic medication, compared to 24.4% in the control group. Among women taking second-generation antipsychotic medications, 59.3% reported breastfeeding, compared to 88.2% in the control group. Three months postpartum, 23% of women taking second-generation antipsychotic medications were exclusively breastfeeding, compared to 47% in the control group. The number of women taking quetiapine was not reported. One woman started taking quetiapine four weeks postpartum to treat obsessive thoughts. She took 50 mg every night at 11 pm after her last breastfeeding. For the next six months, she experienced tingling and milk ejection approximately 30 to 40 minutes after taking the medication each night. One night she did not take the medication and did not experience milk ejection. The milk ejection recurred the following night after she resumed taking the medication. The lactation may have been caused by quetiapine.

---

In the acute toxicity test in rats, the oral LD50 of quetiapine fumarate (ICI 204636) was 1850 mg/kg, and the intraperitoneal LD50 was 750 mg/kg [1]
In clinical application, common adverse reactions are drowsiness (incidence rate 32%), dizziness (21%) and weight gain (18%), most of which are mild to moderate and can be relieved with the progress of treatment [1]
In patients treated for a long time (12 months), no obvious abnormalities were found in liver and kidney function or blood routine indicators, and no obvious extrapyramidal reactions (incidence rate <5%) were observed [1]
When used in combination with CYP3A4 inhibitors (such as ketoconazole), the drug clearance rate decreased by 40%, and the dose needed to be reduced; when used in combination with CYP3A4 inducers (such as carbamazepine), the clearance rate increased by 2.5 times, and the dose needed to be increased [1]
No obvious cardiovascular toxicity was observed, and the blood pressure and heart rate of patients remained stable during treatment [1]

[1]. J Clin Psychiatry. 2002:63 Suppl 13:5-11.

[2]. Hippocampus. 2006;16(6):551-9.

[3]. Brain Res. 2005 Nov 23;1063(1):32-9.

Quetiapine fumarate is the fumarate form of quetiapine, a dibenzothiazole derivative with antipsychotic activity. Quetiapine fumarate antagonizes serotonin activity mediated by 5-HT1A and 5-HT2 receptors. While it has a low affinity for serotonin, it can reversibly bind to dopamine D1 and D2 receptors in the mesolimbic and mesocortical regions of the brain, thereby alleviating psychotic symptoms such as hallucinations and delusions. Furthermore, quetiapine fumarate can also bind to other α1, α2 adrenergic receptors and histamine H1 receptors.
A dibenzothiazole antipsychotic drug targeting the serotonin 5-HT2 receptor; it acts on histamine H1 receptors, adrenergic α1 and α2 receptors, and dopamine D1 and D2 receptors. Used to treat schizophrenia, bipolar disorder, and depression.
See also: Quetiapine (containing the active ingredient). Quetiapine is a dibenzothiazole, N-alkylpiperazine, and N-arylpiperazine compound. It acts as a serotonergic antagonist, dopaminergic antagonist, histamine antagonist, adrenergic antagonist, and second-generation antipsychotic. Quetiapine was initially approved by the FDA in 1997 as a second-generation atypical antipsychotic for the treatment of schizophrenia, major depressive disorder, and bipolar disorder. Quetiapine has high therapeutic efficacy and a low risk of adverse reactions with long-term treatment. It is well-tolerated and is a suitable option for some patients who are highly sensitive to other medications such as clozapine and olanzapine. Quetiapine is an atypical antipsychotic. Quetiapine is an atypical antipsychotic used to treat schizophrenia and bipolar disorder. Use of quetiapine is associated with elevated serum transaminases, and in rare cases, can lead to clinically significant acute liver injury. Quetiapine fumarate is the fumarate form of quetiapine, a dibenzothiazoline derivative with antipsychotic activity. Quetiapine fumarate antagonizes serotonin activity mediated by 5-HT1A and 5-HT2 receptors. This drug has a low affinity for dopamine D1 and D2 receptors, but reversibly binds to them in the mesolimbic system and midbrain cortex, thereby alleviating psychotic symptoms such as hallucinations and delusions. Furthermore, quetiapine fumarate can also bind to other α1, α2 adrenergic receptors and histamine H1 receptors. The most common side effect is sedation, therefore it is often used to treat patients with sleep disorders. Seroquel induces drowsiness and helps patients fall asleep. It is one of the most potent sedatives of all antipsychotics, comparable even to some of the most potent older antipsychotics. Due to its sedative effect, many prescriptions require the full dose to be taken before bedtime. Although quetiapine is FDA-approved for the treatment of schizophrenia and bipolar disorder, it is frequently used for off-label purposes, such as treating insomnia or anxiety. Due to its sedative side effects, there have been reports in the medical literature of quetiapine abuse (sometimes by crushing the tablet and inhaling it through the nose); quetiapine belongs to the atypical antipsychotic class, which has become an increasingly popular alternative to traditional antipsychotics such as haloperidol. Quetiapine is approved for the treatment of acute manic episodes in schizophrenia and bipolar disorder. It is also used to treat other conditions such as post-traumatic stress disorder, alcoholism, obsessive-compulsive disorder, anxiety, hallucinations in Parkinson's patients after taking ropinirole, and as a sedative for sleep disorders. The most common side effect is sedation, so it is often used to treat patients with sleep disorders. Quetiapine makes patients drowsy and helps them fall asleep. It is one of the most potent sedatives of all antipsychotics, even comparable to some of the most potent older antipsychotics. Due to its sedative effect, many prescriptions require the full dose to be taken at bedtime. Although quetiapine is approved by the U.S. Food and Drug Administration (FDA) for the treatment of schizophrenia and bipolar disorder, it is often used for off-label purposes, such as for insomnia or anxiety. Due to its sedative side effects, there have been reports in the medical literature of quetiapine abuse (sometimes by inhaling crushed tablets); for the same reason, other antipsychotics, such as chlorpromazine (Thorazine), may also be abused, but research on typical antipsychotic abuse is limited. Quetiapine is a dibenzothiazole antipsychotic that targets the serotonin 2 receptor; it acts on histamine H1 receptors, adrenergic α1 and α2 receptors, and dopamine D1 and dopamine D2 receptors. It is used to treat schizophrenia, bipolar disorder, and depression.
See also: Quetiapine fumarate (in salt form).
Drug Indications
Quetiapine is used for the symptomatic treatment of schizophrenia. Additionally, it can be used to treat acute manic or mixed episodes in patients with type I bipolar disorder, either as monotherapy or in combination with other medications. It can be used to treat depressive episodes of bipolar disorder. In addition to the above indications, quetiapine can be used in combination with antidepressants to treat major depressive disorder. Some non-indications for this drug include the treatment of post-traumatic stress disorder (PTSD), generalized anxiety disorder, and psychosis associated with Parkinson's disease.
FDA Label
Mechanism of Action
Although the mechanism of action of quetiapine is not fully elucidated, several possible mechanisms have been proposed. In schizophrenia, its action may derive from antagonism of dopamine type 2 (D2) receptors and serotonin type 2A (5HT2A) receptors. In bipolar and major depressive disorder, the effects of quetiapine may be attributed to the binding of the drug or its metabolites to norepinephrine transporters. Other effects of quetiapine, including somnolence, orthostatic hypotension, and anticholinergic effects, may stem from its antagonism of H1 receptors, adrenergic α1 receptors, and muscarinic M1 receptors, respectively. The therapeutic effects of antipsychotic drugs are thought to be achieved by blocking dopaminergic pathways in the mesolimbic system and mesocortical regions of the central nervous system (CNS), and its antidopaminergic effects in the neostriatum appear to be associated with extrapyramidal reactions. The low incidence of extrapyramidal reactions associated with quetiapine treatment suggests that the drug is more active in the mesolimbic dopaminergic system than in the neostriatal dopaminergic system. Unlike typical antipsychotics (e.g., chlorpromazine), but similar to other atypical antipsychotics (e.g., clozapine), quetiapine does not cause a sustained increase in serum prolactin levels, and therefore is unlikely to cause adverse reactions such as amenorrhea, galactorrhea, and impotence. The mechanism of action of quetiapine in antipsychotic activity is not fully elucidated, but it may involve antagonism of serotonin type 1 (5-HT1A) and type 2 (5-HT2A, 5-HT2C) receptors, as well as dopamine (D1, D2) receptors. Current evidence suggests that the clinical efficacy and antipsychotic effects of typical and atypical antipsychotics are generally related to their affinity for and blockade of central dopamine D2 receptors; however, dopamine D2 receptor antagonism does not appear to fully explain the antipsychotic effects of quetiapine. In vivo and in vitro studies indicate that quetiapine's antagonistic effect on dopamine D2 receptors is relatively weak. Receptor binding studies show that quetiapine's antagonistic effect on D1 receptors is also weak. Although the mechanisms of action of dopamine D3, D4, and D5 receptors in inducing the pharmacological effects of antipsychotics are not fully understood, these receptors have been identified; quetiapine has no affinity for dopamine D4 receptors. Quetiapine possesses α1 and α2 adrenergic blocking activity; the blocking effect on α1 adrenergic receptors may explain the occasional orthostatic hypotension caused by the drug. Quetiapine also blocks histamine H1 receptors, which may explain its sedative effect. Quetiapine has almost no affinity for β-adrenergic receptors, γ-aminobutyric acid (GABA) receptors, benzodiazepine receptors, or muscarinic receptors. Recent neuroimaging and autopsy studies have reported abnormalities in the white matter of the brains of schizophrenic patients, suggesting that oligodendrocytes may be involved in the pathogenesis of schizophrenia. Gene chip studies also support this view, showing that, compared with controls, the expression of genes related to oligodendrocyte function and myelination was downregulated in the brains of schizophrenic patients. However, current information on the response of oligodendrocytes to antipsychotic drugs (APDs) remains limited, and this information is crucial for validating the oligodendrocyte hypothesis. This study found that: (1) quetiapine (QUE, an atypical antipsychotic) combined with growth factor treatment increased the proliferation of neural progenitor cells isolated from the cerebral cortex of embryonic rats; (2) QUE guided the differentiation of neural progenitor cells into oligodendrocyte lineages through extracellular signal-regulated kinases; (3) the addition of QUE increased the synthesis of myelin basic protein and promoted myelin formation in rat embryonic cortical aggregate cultures; and (4) long-term administration of QUE to C57BL/6 mice prevented cortical demyelination and associated spatial working memory impairment induced by the neurotoxin copper azine. These findings suggest a novel neural mechanism of quetiapine's antipsychotic effect and contribute to determining the role of oligodendrocytes in the etiology, pathology, and treatment of schizophrenia. Quetiapine fumarate (ICI 204636) is an atypical antipsychotic drug that exerts its pharmacological effects through multi-receptor regulation (dopamine, serotonin, histamine, and adrenergic receptors). It is effective for both positive and negative symptoms of schizophrenia [1]. Its central nervous system protective mechanism is related to enhancing hippocampal synaptic plasticity and regulating the balance of glutamate-GABA neurotransmitters, thereby improving cognitive dysfunction [2][3]. Clinical indications include schizophrenia, manic episodes of bipolar disorder, and it can also be used as an adjunct therapy for depression (as an synergist) [1]. Compared with traditional antipsychotic drugs, this drug has a lower incidence of extrapyramidal reactions and better tolerability, making it suitable for long-term maintenance therapy [1]. It is administered orally and is available in two dosage forms: regular tablets and extended-release formulations. The extended-release formulation is taken once daily, resulting in higher patient compliance [1].

C46H54N6O8S2

883.09

882.34

C, 62.56; H, 6.16; N, 9.52; O, 14.49; S, 7.26

111974-72-2

Quetiapine; 111974-69-7; Quetiapine-d4 hemifumarate; 1217310-65-0; Quetiapine sulfoxide dihydrochloride; 329218-11-3; Quetiapine hemifumarate (Standard); 111974-72-2; Quetiapine-d4 fumarate; 1287376-15-1; Quetiapine-d8 fumarate; 1185247-12-4; Quetiapine-d8 hemifumarate; Quetiapine hemifumarate-d8; 1435938-24-1; Quetiapine sulfoxide; 329216-63-9

5281025

White to off-white solid powder

556.5ºC at 760 mmHg

174-176°C

290.4ºC

3.22E-13mmHg at 25°C

4.046

4

14

14

62

615

0

C1CN(CCN1CCOCCO)C2=NC3=CC=CC=C3SC4=CC=CC=C42.C1CN(CCN1CCOCCO)C2=NC3=CC=CC=C3SC4=CC=CC=C42.C(=C/C(=O)O)\C(=O)O

ZTHJULTYCAQOIJ-WXXKFALUSA-N

InChI=1S/2C21H25N3O2S.C4H4O4/c2*25-14-16-26-15-13-23-9-11-24(12-10-23)21-17-5-1-3-7-19(17)27-20-8-4-2-6-18(20)22-21;5-3(6)1-2-4(7)8/h2*1-8,25H,9-16H2;1-2H,(H,5,6)(H,7,8)/b;;2-1+

2-[2-(4-benzo[b][1,4]benzothiazepin-6-ylpiperazin-1-yl)ethoxy]ethanol;(E)-but-2-enedioic acid

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: Please store this product in a sealed and protected environment, avoid exposure to moisture.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Solubility in Formulation 1: ≥ 2.5 mg/mL (5.66 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

---

Solubility in Formulation 2: ≥ 2.5 mg/mL (5.66 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

---

View More

Solubility in Formulation 3: ≥ 2.5 mg/mL (5.66 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

---

Solubility in Formulation 4: 0.5% CMC Na: 30mg/mL

---

 (Please use freshly prepared in vivo formulations for optimal results.)