Кветиапин

Labelled Quetiapine (Q510000). Used as an antipsychotic.

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.

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.

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.