Quetiapine: preclinical studies, pharmacokinetics, drug interactions, and dosing.
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. In animal models, the drug has a preclinical profile suggestive of antipsychotic activity with a reduced tendency to cause extrapyramidal symptoms (EPS) and sustained prolactin elevation. For example, quetiapine alters neurotensin neurotransmission and c-fos expression in limbic but not motor brain regions. The drug also demonstrates clozapine-like activity in a range of behavioral and biochemical tests and may possess neuroprotective properties. In humans, quetiapine exhibits linear pharmacokinetics with a mean terminal half-life of 7 hours. The primary route of elimination of quetiapine is through hepatic metabolism. Although not affected by smoking, alterations in quetiapine disposition due to age or hepatic impairment are manageable by appropriate dosage reduction. The optimal dosing range for quetiapine is 150 to 750 mg/day, and recent results suggest that once-daily dosing may be suitable for some patients. Finally, imaging studies with positron emission tomography confirm significant differences between quetiapine and typical antipsychotics that may be indicative of their differences in mechanism of action and propensity for producing EPS.
Nemeroff
Charles B
CB
Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA 30322-4990, USA. cnemero@emory.edu
Kinkead
Becky
B
Goldstein
Jeffrey
J
D000818:Animals; D014150:Antipsychotic Agents / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D001522:Behavior, Animal / Q000187:drug effects; D003987:Dibenzothiazepines / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004347:Drug Interactions; D015870:Gene Expression / Q000187:drug effects; D017781:Genes, Immediate-Early / Q000187:drug effects / Q000502:physiology; D006801:Humans; D066298:In Vitro Techniques; D011618:Psychotic Disorders / Q000188:drug therapy / Q000523:psychology; D000069348:Quetiapine Fumarate; D017981:Receptors, Neurotransmitter / Q000187:drug effects / Q000378:metabolism; D014055:Tomography, Emission-Computed
D014150:Antipsychotic Agents; D003987:Dibenzothiazepines; D017981:Receptors, Neurotransmitter; D000069348:Quetiapine Fumarate