Occupancy of striatal D-2-like dopamine receptors after treatment with thesigma ligand EMD 57445, a putative atypical antipsychotic

Rationale: EMD 57445 (panamesine) is a high affinity sigma ligand with the profile of an atypical antipsychotic in animal studies. It has been reporte d recently to have antipsychotic activity in schizophrenia. However, its me tabolite, EMD 59983, binds also to D-2 and D-3 dopamine (DA) receptors. Obj ectives: The aim of this study was to test, using single photon emission co mputed tomography (SPECT) and [I-123]iodobenzamide (IBZM) as the radiotrace r, whether EMD 59983 would pass the blood-brain barrier and to what extent it would contribute to the effects of EMD 57445 in schizophrenia. Methods: Two IBZM SPECT-scans were performed in five neuroleptic-free schizophrenic patients (DSM IV), one before and one after treatment with 60 mg panamesine daily for a treatment duration of 12-26 days. Results: A high occupancy of striatal D-2-like DA receptors similar to that induced by typical neurolep tics was observed in all patients treated with EMD 57445. Conclusions: Our results suggest that a possible antipsychotic activity of EMD 57445 in schi zophrenia is not necessarily attributable to its affinity for sigma recepto rs, but could be simply due to the potent antidopaminergic effects of EMD 5 9983, its main metabolite.