title: Striatal and frontal cortex binding of 11-C-labelled clozapine visualized by positron emission tomography (PET) in drug-free schizophrenics and healthy volunteers.
abstract: The binding of 11C-labelled clozapine in the brain was studied in three drug-free schizophrenic patients and in three healthy volunteers. High radioactivities were found in the striatum and in the frontal cortex. The rate constant k3, which is proportional to receptor association rate and the number of receptors, was lower in the frontal cortex compared to the striatum. No obvious difference between the two brain areas was seen for the dissociation rate constant from the receptors (k4). Two schizophrenic patients were reexamined after pretreatment with haloperidol, one after 6 weeks of treatment with a low oral dose, the other one after an IV injection 1 h before 11C-clozapine was given. After haloperidol pretreatment, the binding of 11C-clozapine in striatum and frontal cortex was reduced, more pronounced in the striatum, indicating competition for D-2 dopamine binding sites. Our finding indicates that clozapine has an affinity for a receptor population in the frontal cortex that is predominantly not of the dopamine-D2 type. This feature might be of importance for the unique clinical profile of the drug.
authors.affiliation: Psychiatric Research Center, Ulleråker Hospital, Uppsala, Sweden.
authors.forename: T
authors.initials: T
authors.lastname: Lundberg
authors.forename: L H
authors.initials: LH
authors.lastname: Lindström
authors.forename: P
authors.initials: P
authors.lastname: Hartvig
authors.forename: S A
authors.initials: SA
authors.lastname: Eckernâs
authors.forename: B
authors.initials: B
authors.lastname: Ekblom
authors.forename: H
authors.initials: H
authors.lastname: Lundqvist
authors.forename: K J
authors.initials: KJ
authors.lastname: Fasth
authors.forename: P
authors.initials: P
authors.lastname: Gullberg
authors.forename: B
authors.initials: B
authors.lastname: Långström
mesh_terms: D000328:Adult; D002250:Carbon Radioisotopes; D003024:Clozapine / Q000493:pharmacokinetics*; D003342:Corpus Striatum / Q000378:metabolism*; D003984:Dibenzazepines / Q000493:pharmacokinetics*; D005625:Frontal Lobe / Q000378:metabolism*; D006220:Haloperidol / Q000494:pharmacology; D006801:Humans; D008297:Male; D011954:Receptors, Dopamine / Q000378:metabolism / Q000502:physiology; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D012559:Schizophrenia / Q000378:metabolism*; D014055:Tomography, Emission-Computed
chemical_list: D002250:Carbon Radioisotopes; D003984:Dibenzazepines; D011954:Receptors, Dopamine; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D003024:Clozapine; D006220:Haloperidol