| 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. |
| Authors | V Bigliani, R S Mulligan, P D Acton, R I Ohlsen, V W Pike, P J Ell, S Gacinovic, R W Kerwin, L S Pilowsky
(Affiliation: Institute of Psychiatry, De Crespigny Park, Denmark Hill, London, UK.)
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| Journal | Psychopharmacology
(Psychopharmacology (Berl))
Vol. 150
Issue 2
Pg. 132-40
(Jun 2000)
ISSN: 0033-3158 GERMANY |
| PMID | 10907666
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
|
| Chemical References |
- Antipsychotic Agents
- Benzamides
- Benzodiazepines
- DRD3 protein, human
- Imidazoles
- Indoles
- Iodine Radioisotopes
- Pyrrolidines
- Receptors, Dopamine D2
- Receptors, Dopamine D3
- sertindole
- epidepride
- olanzapine
- Pirenzepine
|
| Topics |
- Adult
- Analysis of Variance
- Antipsychotic Agents
(pharmacokinetics)
- Benzamides
(pharmacokinetics)
- Benzodiazepines
- Corpus Striatum
(metabolism)
- Female
- Humans
- Imidazoles
(pharmacokinetics)
- Indoles
(pharmacokinetics)
- Iodine Radioisotopes
(pharmacokinetics)
- Male
- Middle Aged
- Pirenzepine
(analogs & derivatives, pharmacokinetics)
- Pyrrolidines
(pharmacokinetics)
- Receptors, Dopamine D2
(metabolism)
- Receptors, Dopamine D3
- Schizophrenia
(metabolism)
- Temporal Lobe
(metabolism)
- Tomography, Emission-Computed
|
