Is amoxapine an atypical antipsychotic?: Positron-emission tomography investigation of its dopamine2 and serotonin2 occupancy

Background: All currently available atypical antipsychotics have, at clinically relevant doses: i) high serotonin (5-HT)(2) occupancy; ii) greater 5-HT2 than dopamine (D)(2) occupancy; and iii) a higher incidence of extrapyramidal side effects when their D-2 occupancy exceeds 80%. A review of pharmacologic and behavioral data suggested that amoxapine should also conform to this profile; therefore, we undertook a positron-emission tomography (PET) study of its 5-HT2 and D-2 occupancy. Methods: Seven healthy volunteers received 50-250 mg/day of amoxapine for 5 days and then had [C-11]-raclo-pride and [F-18]-setoperone PET scans. Results: 5-HT2 receptors showed near saturation at doses of 100 mg/day and above. The D-2 receptor occupancies showed a dose-dependent increase, never exceeding 80%; at all doses 5-HT2 occupancy exceeded D-2 occupancy. Conclusions: PET data show that amoxapine's profile is very similar to that of the established atypical antipsychotics, These data, together with amoxapine's in vitro pharmacologic profile, effectiveness in animal models, and efficacy in psychotic depression raise the possibility of amoxapine as an "atypical" antipsychotic agent in the treatment of schizophrenia, (C) 1999 Society of Biological Psychiatry.