Striatal and temporal cortical D2/D3 receptor occupancy by olanzapine and sertindole in vivo: a [123I]epidepride single photon emission tomography (SPET) study.
Psychopharmacology (Berl)
; 150(2): 132-40, 2000 Jun.
Article
de En
| MEDLINE
| ID: mdl-10907666
ABSTRACT
RATIONALE Previous work suggests clozapine preferentially targets limbic cortical dopamine systems, which could help account for its lack of extrapyramidal side effects (EPS) and superior therapeutic efficacy. OBJECTIVES:
To test the hypothesis that olanzapine, a novel atypical antipsychotic drug, occupies temporal cortical D2/D3 receptors to a greater extent than striatal D2/D3 receptors in vivo.METHODS:
Nine schizophrenic patients taking either olanzapine [(n=5; mean (SD) age 32.5 (6.5) years; daily dose 18.3 (2.6) mg] or sertindole [(n=4; mean (SD) age 30.3 (7.4) years; daily dose 16 (5.6) mg] were studied with [123I]epidepride ((S)-N-[(1-ethyl-2-pyrrolidinyl)methyl]-5-iodo-2,3-dimethoxybenz amide) and single photon emission tomography (SPET). An estimate of [123I]epidepride 'specific binding' to D2/D3 receptors was obtained in patients and age-matched healthy volunteers. A summary measure was generated representing striatal and temporal cortical relative %D2/D3 receptor occupancy by antipsychotic drugs. Occupancy data were compared with previously studied groups of patients receiving typical antipsychotic drugs (n=12) and clozapine (n=10).RESULTS:
Mean striatal and temporal cortical %D2/D3 receptor occupancy in olanzapine-treated patients was 41.3% (SD 17.9) and 82.8% (SD 4.2), respectively. Unexpectedly low levels of striatal relative %D2/D3 receptor occupancy were seen in two patients with typical antipsychotic-drug-induced movement disorder prior to switching to olanzapine. In the temporal cortex, mean D2/D3 dopamine receptor occupancy levels above 80% were seen for all antipsychotic drugs studied.CONCLUSIONS:
The atypical antipsychotic drugs olanzapine and sertindole, in common with clozapine, demonstrate higher occupancy of temporal cortical than striatal D2/D3 dopamine receptors in vivo at clinically useful doses. This could help mediate their atypical clinical profile of therapeutic efficacy with few extrapyramidal side effects. Limbic selective blockade of D2/D3 dopamine receptors could be a common action of atypical antipsychotic drugs.
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Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Neuroleptiques
/
Pirenzépine
/
Récepteur D2 de la dopamine
/
Imidazoles
/
Indoles
Limites:
Adult
/
Female
/
Humans
/
Male
/
Middle aged
Langue:
En
Journal:
Psychopharmacology (Berl)
Année:
2000
Type de document:
Article
Pays d'affiliation:
Royaume-Uni