Abstract:
RATIONALE:Atypical antipsychotic drugs are classically associated with lower propensity to extrapyramidal symptoms (EPS) and hyperprolactinemia than typical antipsychotic drugs. It has not been clarified why some atypical antipsychotic drugs, such as amisulpride, induce prolactin plasma concentration (PRL) elevation, but little EPS. Previous studies have found an association between striatal D2/D3 receptor occupancy and PRL in typical antipsychotic treated patients suggesting that PRL is a marker of central D2/D3 receptors blockade. OBJECTIVE:We have evaluated the relationship between PRL and central (striatum, temporal cortex and thalamus) D2/D3 receptor occupancy in amisulpride treated schizophrenic patients. METHODS:Single photon emission tomography (SPET) and [123I]-epidepride were used to determine D2/D3 receptor occupancy in eight amisulpride treated patients. PRL was measured concurrently with the scans. RESULTS:The mean PRL was 1166 (range 499-1892 mIU/l) for a mean amisulpride dose of 406 mg/day (range 150-600 mg/day). Amisulpride plasma concentration and central D2/D3 receptor occupancy were positively correlated (r=0.83-0.89, df=4, P<0.05). No significant correlations were observed between PRL and amisulpride (daily dose or plasma concentration, P>0.05), or between PRL and central D2/D3 receptor occupancy (P>0.05). CONCLUSIONS:Our findings show that amisulpride-induced hyperprolactinemia is uncoupled from central D2/D3 receptor occupancy. Amisulpride has poor blood-brain barrier penetration and reaches much higher concentration at the pituitary, which is outside the blood-brain barrier. Higher D2/D3 receptor occupancy at the pituitary gland than at central regions is a possible explanation for amisulpride PRL elevation with low EPS. Further studies evaluating pituitary D2/D3 receptor occupancy in vivo are necessary to confirm this hypothesis.
journal_name
Psychopharmacology (Berl)journal_title
Psychopharmacologyauthors
Bressan RA,Erlandsson K,Spencer EP,Ell PJ,Pilowsky LSdoi
10.1007/s00213-004-1826-6subject
Has Abstractpub_date
2004-09-01 00:00:00pages
367-73issue
3eissn
0033-3158issn
1432-2072journal_volume
175pub_type
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更新日期:1987-01-01 00:00:00
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更新日期:1999-05-01 00:00:00
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更新日期:1984-01-01 00:00:00
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更新日期:2017-02-01 00:00:00
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更新日期:2010-03-01 00:00:00
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更新日期:2008-05-01 00:00:00