Quetiapine Chemical Properties

Melting point:

172-173 °C

Boiling point:

556.5±60.0 °C(Predicted)

Density 

1.27±0.1 g/cm3(Predicted)

storage temp. 

Store at -20°C

solubility 

H2O : < 0.1 mg/mL (insoluble)

form 

Powder

pka

14.41±0.10(Predicted)

color 

Light yellow to yellow

Stability:

Very Hygroscopic

LogP

0.899

CAS DataBase Reference

111974-69-7(CAS DataBase Reference)

Safety Information

Hazardous Substances Data

111974-69-7(Hazardous Substances Data)

Quetiapine Usage And Synthesis

Uses

antiviral

Uses

Labelled Quetiapine (Q510000). Used as an antipsychotic.

Definition

ChEBI: Quetiapine is a dibenzothiazepine, a N-alkylpiperazine and a N-arylpiperazine. It has a role as a serotonergic antagonist, a dopaminergic antagonist, a histamine antagonist, an adrenergic antagonist and a second generation antipsychotic.

brand name

Seroquel (AstraZeneca).

Biological Functions

Quetiapine is a dibenzothiazepine with a brain receptor–binding profile similar to that of clozapine. Quetiapine binds most effectively to histaminergic H1, adrenergic a1 and a2, and serotonergic 5-HT2A receptors in the brain and has even lower affinity than clozapine for dopaminergic D2 receptors. Unlike clozapine, however, quetiapine also has very low affinity for muscarinic receptors.

General Description

Quetiapine, 2-[2-(4-dibenzo[b,f][1,4]thiazepin-11-yl-1-piperazinyl)ethoxy]-ethanol fumarate (2:1,salt) (Seroquel), is a white to off-white crystalline powderthat is moderately water soluble. Quetiapine is rapidly absorbed,and peak plasma levels occur 1 to 2 hours after administration.Food does not appreciably affect the absorptionof quetiapine. The compound is 83% bound to plasma proteinsand it has a mean elimination half-life of 7 hours.Administration of a single dose of 14C-quetiapine showedthat only 1% of the drug was excreted unchanged, with 73%excreted into the urine and approximately 30% excreted inthe feces.Numerous metabolites of quetiapine are known,and the sulfoxide metabolite represents the major metabolitepresent in plasma. This metabolite is pharmacologicallyinactive. The remaining metabolites represent only5% of the total radioactivity found in plasma. The 7-hydroxyand the 7-hydroxy-N-desalkyl are active metabolites, but because of their low concentrations in plasma are not thoughtto contribute to the overall effects of quetiapine.
Common side effects associated with quetiapine therapyare orthostatic hypotension and somnolence. These effects are presumably caused by -adrenergic and histamine H₁ receptorblockade, respectively. As with other atypical antipsychotics,patients treated with quetiapine should be monitoredfor hyperglycemic symptoms. Also, children and adolescentswith major depressive disorder may experience an increase intheir depression or suicidal tendencies.typical antipsychotics such as chlorpromazine.This findingmay explain the lack of EPS associated with quetiapine.

Clinical Use

Schizophrenia
Mania in bipolar disorder
Depression in bipolar disorder

Side effects

Quetiapine is 100% bioavailable, but first-pass metabolism yields at least 20 metabolites via CYP3A4, with a half-life of approximately 6 hours. Quetiapine is about as effective as haloperidol in treating the positive symptoms of schizophrenia, but it also manages negative symptoms and induces a lower incidence of extrapyramidal side effects.

Drug interactions

Potentially hazardous interactions with other drugs
Anaesthetics: enhanced hypotensive effect.
Analgesics: increased risk of convulsions with tramadol; enhanced hypotensive and sedative effects with opioids; increased risk of ventricular arrhythmias with methadone.
Anti-arrhythmics: increased risk of ventricular arrhythmias.
Antibacterials: concentration possibly increased by macrolides - avoid.
Antidepressants: concentration of tricyclics possibly increased.
Antiepileptics: antagonism of convulsive threshold; metabolism accelerated by carbamazepine and phenytoin; concentration possibly increased by valproate.
Antifungals: concentration possibly increased by imidazoles and triazoles - avoid.
Antimalarials: manufacturer advises avoid use with artemether and lumefantrine.
Antipsychotics: possible increased risk of ventricular arrhythmias with risperidone.
Antivirals: concentration possibly increased by atazanavir, boceprevir, darunavir, fosamprenavir, indinavir, lopinavir, ritonavir, saquinavir, telaprevir and tipranavir - avoid.
Anxiolytics and hypnotics: enhanced sedative effects.
Atomoxetine: increased risk of ventricular arrhythmias.
Cytotoxics: increased risk of ventricular arrhythmias with arsenic trioxide.
Grapefruit juice: concentration of quetiapine possibly increased - avoid.

Metabolism

Quetiapine is extensively metabolised in the liver by sulfoxidation mediated mainly by the cytochrome P450 isoenzyme CYP3A4 and by oxidation. The primary metabolite is norquetiapine, which is also eliminated by CYP3A4. Following the administration of radiolabelled quetiapine, the parent compound accounted for less than 5% of unchanged drug-related material in the urine or faeces. Approximately 73% of the radioactivity is excreted in the urine and 21% in the faeces, mainly as inactive metabolites.

Quetiapine(111974-69-7)Related Product Information

• DIBENZO[B,F][1,4]THIAZEPINE, 11-OXO-10,11-DIHYDRO- (INTERMEDIATES OF QUETIAPINE)
• Quetiapine fumarate
• Quetiapine Sulfoxide
• 2-[2-(4-Dibenzo[b,f][1,4]thiazepin-11-yl-1-piperazinyl)ethoxy]ethanol N-Oxide,Quetiapine N-Oxide
• Quetiapine IMpurity P (11-(4-Ethylpiperazin-1-yl)dibenzo[b,f][1,4]thiazepine fuMarate))
• Quetiapine EP Impurity N DiHCl
• dibenzo[b,f][1,4]thiazepin-11-amine
• Quetiapine EP Impurity W
• Quetiapine Sulfone
• Quetiapine Impurity E
• Quetiapine EP Impurity N
• Quetiapine EP Impurity C
• 11-(1-Piperazinyl)-dibenzo[b,f][1,4]thiazepine dihydrochloride
• Quetiapine EP Impurity J
• Quetiapine IMpurity T (Quetiapine Morpholine IMpurity)
• Quetiapine EP Impurity Q
• Quetiapine EP Impurity K
• Phenyl2-(Phenylthio)Phenylcarbamate