Prolactinemia is uncoupled from central D-2/D-3 dopamine receptor occupancy in amisulpride treated patients

Prolactinemia is uncoupled from central D-2/D-3 dopamine receptor occupancy in amisulpride treated patients

Author Bressan, R. A. Google Scholar
Erlandsson, K. Google Scholar
Spencer, E. P. Google Scholar
Ell, P. J. Google Scholar
Pilowsky, L. S. Google Scholar
Institution Universidade Federal de São Paulo (UNIFESP)
Univ London Kings Coll
UCL Med Sch
Guys & St Thomas Hosp Trust
Abstract 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 D-2/D-3 receptor occupancy and PRL in typical antipsychotic treated patients suggesting that PRL is a marker of central D-2/D-3 receptors blockade. Objective: We have evaluated the relationship between PRL and central (striatum, temporal cortex and thalamus) D-2/D-3 receptor occupancy in amisulpride treated schizophrenic patients. Methods: Single photon emission tomography (SPET) and [I-123]-epidepride were used to determine D-2/D-3 receptor occupancy in eight amisulpride treated patients. PRL was measured concurrently with the scans. Results: the mean PRL was 1166 (range 499-1892 mIU/1) for a mean amisulpride dose of 406 mg/day (range 150-600 mg/day). Amisulpride plasma concentration and central D-2/D-3 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 D-2/D-3 receptor occupancy (P>0.05). Conclusions: Our findings show that amisulpride-induced hyperprolactinemia is uncoupled from central D-2/D-3 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 D-2/D-3 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 D-2/D-3 receptor occupancy in vivo are necessary to confirm this hypothesis.
Keywords prolactin
antipsychotic agents
atypical antipsychotic
neuroleptic
dopamine receptor
D-2-dopamine
schizophrenia
SPECT
[I-123]-epidepride
amisulpride
photon emission tomography
Language English
Date 2004-09-01
Published in Psychopharmacology. New York: Springer, v. 175, n. 3, p. 367-373, 2004.
ISSN 0033-3158 (Sherpa/Romeo, impact factor)
Publisher Springer
Extent 367-373
Origin http://dx.doi.org/10.1007/s00213-004-1826-6
Access rights Closed access
Type Article
Web of Science ID WOS:000224527000012
URI http://repositorio.unifesp.br/handle/11600/27907

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