| Indication |
For the treatment of schizophrenia and related psychotic disorders. |
| Pharmacodynamics |
Quetiapine is a psychotropic agent belonging to the chemical
class of benzisoxazole derivatives and is indicated for the treatment of
schizophrenia. Quetiapine is a selective monoaminergic antagonist with
high affinity for the serotonin Type 2 (5HT2), and dopamine type 2 (D2) receptors. Quetiapine is an antagonist at serotonin 5-HT1A and 5HT2,
dopamine D1 and D2, histamine H1, and adrenergic alpha 1 and alpha 2
receptors. Quetiapine has no significant affinity for cholinergic
muscarinic or benzodiazepine receptors. Drowsiness and orthostatic
hypotension associated with use of quetiapine may be explained by its
antagonism of histamine H1 and adrenergic alpha 1 receptors,
respectively. Quetiapine's antagonism of adrenergic a1 receptors may
explain the orthostatic hypotension observed with this drug. |
| Mechanism of action |
Quetiapine's antipsychotic activity is likely due to a combination
of antagonism at D2 receptors in the mesolimbic pathway and 5HT2A
receptors in the frontal cortex. Antagonism at D2 receptors relieves
positive symptoms while antagonism at 5HT2A receptors relieves negative
symptoms of schizophrenia. |
| Absorption |
Rapidly and well absorbed. |
| Volume of distribution |
|
| Protein binding |
83% |
| Metabolism |
Hepatic. The major metabolic pathways are sulfoxidation,
mediated by cytochrome P450 3A4 (CYP3A4), and oxidation of the terminal
alcohol to a carboxylic acid. The major sulfoxide metabolite of
quetiapine is inactive. Quetiapine also undergoes hydroxylation of the
dibenzothiazepine ring, O-deakylation, N-dealkylation, and phase II
conjugation. The 7-hydroxy and 7-hydroxy-
N-delakylated metabolites appear to be active, but are present in very
low concentrations. |
| Route of elimination |
Elimination of quetiapine is mainly via hepatic metabolism.
Following a single oral dose of 14C-quetiapine, less than 1% of the
administered dose was excreted as unchanged drug, indicating that
quetiapine is highly metabolized. Approximately 73% and 20% of the dose
was recovered in the urine and feces, respectively. |
| Half life |
6 hours |
| Clearance |
Not Available |
| Toxicity |
Symptoms of overdose include drowsiness and sedation, tachycardia, and hypotension. |
