The D2 receptor occupancy profile of loxapine determined using PET.
Positron emission tomography (PET) studies of typical neuroleptics suggest that 60% to 80% of striatal D2 occupancy may be sufficient for optimal clinical treatment of psychosis. Therefore, striatal D2 occupancy may be used as an index to determine the optimal dose range. Toward this end, we determined the in vivo D2 profile of loxapine, using [11C]-raclopride and PET. Seven patients selected from a clinical population were scanned while taking steady-state oral loxapine from 10 to 100 mg/day. Their D2 receptor occupancy was estimated by comparing them to age-matched data from neuroleptic-naive patients. The D2 receptor occupancy ranged from 52% to 90%, and there was a very strong relationship between dose and D2 occupancy, suggesting that 15 to 30 mg/day of loxapine would produce, the putatively optimal, 60% to 80% striatal D2 blockade. This dose range is much lower than that used in most clinical settings and points to the potential efficacy of loxapine at lower doses.
Kapur
S
S
Schizophrenia Division, Clarke Institute of Psychiatry, Toronto, ON, Canada.
Zipursky
R B
RB
Jones
C
C
Remington
G J
GJ
Wilson
A A
AA
DaSilva
J
J
Houle
S
S
D000284:Administration, Oral; D000328:Adult; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000378:metabolism*; D002250:Carbon Radioisotopes; D003342:Corpus Striatum / Q000378:metabolism; D003430:Cross-Sectional Studies; D018492:Dopamine Antagonists / Q000008:administration & dosage / Q000378:metabolism*; D005260:Female; D006801:Humans; D008152:Loxapine / Q000008:administration & dosage / Q000378:metabolism*; D008297:Male; D011618:Psychotic Disorders / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000378:metabolism*; D020891:Raclopride; D017448:Receptors, Dopamine D2 / Q000187:drug effects*; D012457:Salicylamides; D014055:Tomography, Emission-Computed / Q000379:methods
D014150:Antipsychotic Agents; D002250:Carbon Radioisotopes; D018492:Dopamine Antagonists; D017448:Receptors, Dopamine D2; D012457:Salicylamides; D020891:Raclopride; D008152:Loxapine