Prolactinemia is uncoupled from central D2/D3 dopamine receptor occupancy in amisulpride treated patients.
BACKGROUND
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.
Section of Neurochemical Imaging, Institute of Psychiatry, King's College London, Denmark Hill, London, UK. r.bressan@iop.kcl.ac.uk
Rodrigo A
RA
Bressan
Kjell
K
Erlandsson
Edgar P
EP
Spencer
Peter J
PJ
Ell
Lyn S
LS
Pilowsky
D000328:Adult; D000077582:Amisulpride; D014150:Antipsychotic Agents / Q000009:adverse effects* / Q000378:metabolism; D001921:Brain / Q000378:metabolism; D003287:Contrast Media; D065127:Dopamine D2 Receptor Antagonists; D004361:Drug Tolerance; D005260:Female; D006801:Humans; D006966:Hyperprolactinemia / Q000139:chemically induced*; D008297:Male; D008875:Middle Aged; D011618:Psychotic Disorders / Q000188:drug therapy / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D050637:Receptors, Dopamine D3; D012559:Schizophrenia / Q000188:drug therapy / Q000378:metabolism; D013469:Sulpiride / Q000009:adverse effects* / Q000031:analogs & derivatives* / Q000378:metabolism; D015899:Tomography, Emission-Computed, Single-Photon
D014150:Antipsychotic Agents; D003287:Contrast Media; C493593:DRD3 protein, human; D065127:Dopamine D2 Receptor Antagonists; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D013469:Sulpiride; D000077582:Amisulpride