Non-uniform blockade of intrastriatal D2/D3 receptors by risperidone and amisulpride.
BACKGROUND
Atypical antipsychotic drugs have been shown to preferentially affect extrastriatal (mesolimbic) D2/D3 receptors over those within the striatum (nigrostriatal). The striatum does not contain exclusively nigrostriatal dopamine tracts, however. The caudate nucleus and ventral parts of the striatum primarily contain limbic and associative dopamine pathways more relevant to psychosis.


OBJECTIVE
We tested the hypothesis that two pharmacologically distinct atypical antipsychotic drugs, amisulpride and risperidone, would preferentially occupy of D2/D3 dopamine receptors in limbic and associative regions of the striatum.


METHODS
Eight amisulpride-treated patients, six risperidone-treated patients and six age- and sex-matched healthy controls were recruited. Dynamic SPET studies were performed after bolus injection of [123I]epidepride. Binding potential (BP) images were generated using a modified Logan method and aligned between subjects. Regions of interest (ROIs) were placed around head of caudate and putamen bilaterally on an average BP map derived from aligned control images. These ROIs were then applied user-independently to the BP maps for each subject to calculate BP for head of caudate and putamen. Mean occupancy of D2/D3 receptors in each ROI was determined by reference to the drug-free healthy volunteer group. Occupancy values for head of caudate and putamen were compared using paired Student's t test.


RESULTS
D2/D3 receptor occupancy was 42% in caudate and 31% in putamen for risperidone (t=5.9, df=11, p=0.0001) and 51% in caudate and 37% in putamen for amisulpride (t=11.1, df=15, p<0.0001).


CONCLUSIONS
Amisulpride and risperidone both show selective occupancy for limbic and associative D2/D3 receptors within the striatum.
Stone
James M
JM
Section of Neurochemical Imaging, Institute of Psychiatry, King's College London, De Crespigny Park, Denmark Hill, London, SE5 8AF, UK. j.stone@iop.kcl.ac.uk
Bressan
Rodrigo A
RA
Erlandsson
Kjell
K
Ell
Peter J
PJ
Pilowsky
Lyn S
LS
D000328:Adult; D000077582:Amisulpride; D014150:Antipsychotic Agents / Q000008:administration & dosage; D001549:Benzamides / Q000493:pharmacokinetics; D001667:Binding, Competitive / Q000187:drug effects; D001931:Brain Mapping; D016022:Case-Control Studies; D003342:Corpus Striatum / Q000000981:diagnostic imaging / Q000187:drug effects*; D018492:Dopamine Antagonists / Q000008:administration & dosage*; D065127:Dopamine D2 Receptor Antagonists; D005260:Female; D006801:Humans; D007456:Iodine Isotopes / Q000493:pharmacokinetics; D008297:Male; D011759:Pyrrolidines / Q000493:pharmacokinetics; D050637:Receptors, Dopamine D3 / Q000037:antagonists & inhibitors; D018967:Risperidone / Q000008:administration & dosage*; D012559:Schizophrenia / Q000188:drug therapy; D013469:Sulpiride / Q000008:administration & dosage / Q000031:analogs & derivatives*; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods
D014150:Antipsychotic Agents; D001549:Benzamides; D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; D007456:Iodine Isotopes; D011759:Pyrrolidines; D050637:Receptors, Dopamine D3; C063525:epidepride; D013469:Sulpiride; D000077582:Amisulpride; D018967:Risperidone
Psychopharmacology (Berl). 1996 Mar;124(1-2):57-73
8935801
J Cereb Blood Flow Metab. 1990 Sep;10(5):740-7
2384545
J Comput Assist Tomogr. 1981 Oct;5(5):734-43
6975289
Lancet. 1997 Aug 16;350(9076):490-1
9274589
J Chem Neuroanat. 2003 Dec;26(4):317-30
14729134
Br J Psychiatry. 2000 Nov;177:408-15
11059993
Am J Psychiatry. 2001 Mar;158(3):360-9
11229973
J Comput Assist Tomogr. 1998 Jan-Feb;22(1):153-65
9448780
Arch Gen Psychiatry. 1990 Mar;47(3):213-9
1968328
Neuroscience. 1999 May;90(2):433-45
10215149
Pharmacol Ther. 2001 May-Jun;90(2-3):231-59
11578658
Ann Neurol. 1989 Oct;26(4):551-7
2817829
N Engl J Med. 1988 Apr 7;318(14):876-80
3352672
Life Sci. 1998;62(20):1825-31
9600324
Mov Disord. 2003 Dec;18(12 ):1415-23
14673877
Eur J Neurosci. 1998 Aug;10(8):2565-73
9767387
Br J Psychiatry. 2001 Dec;179:503-8
11731352
Prog Neuropsychopharmacol Biol Psychiatry. 2003 Oct;27(7):1081-90
14642968
Neuroimage. 2003 Jul;19(3):1205-14
12880845
Am J Psychiatry. 2001 Jun;158(6):926-30
11384901
Brain Res Brain Res Rev. 2000 Mar;31(2-3):236-50
10719151
J Psychiatr Res. 1975 Nov;12(3):189-98
1202204
Mov Disord. 1995 Jan;10(1):51-65
7885356
Neuroimage. 1996 Dec;4(3 Pt 1):153-8
9345505
Ann Neurol. 1982 Jul;12(1):52-5
7114818
Ann Neurol. 1995 Mar;37(3):300-12
7695230
Int J Neuropsychopharmacol. 2004 Dec;7(4):421-30
15683553
J Cereb Blood Flow Metab. 2002 Feb;22(2):240-4
11823722
J Pharmacol Exp Ther. 1997 Jan;280(1):83-97
8996185
Trends Pharmacol Sci. 1998 Apr;19(4):136-40
9612088
Eur J Nucl Med Mol Imaging. 2004 Apr;31(4):564-77
14689241
J Nucl Med. 2000 Dec;41(12 ):2083-8
11138696
Neuropsychopharmacology. 1997 Jun;16(6):375-84
9165493
Psychopharmacology (Berl). 1997 Oct;133(4):396-404
9372541
Psychopharmacology (Berl). 2000 Jun;150(2):132-40
10907666
J Clin Psychopharmacol. 2003 Feb;23 (1):5-14
12544369
Brain Res Brain Res Rev. 1997 Feb;23(1-2):62-78
9063587
Am J Psychiatry. 2003 Aug;160(8):1413-20
12900302