title: Occupancy of striatal D(2)-like dopamine receptors after treatment with the sigma ligand EMD 57445, a putative atypical antipsychotic.
abstract: BACKGROUND
  EMD 57445 (panamesine) is a high affinity sigma ligand with the profile of an atypical antipsychotic in animal studies. It has been reported recently to have antipsychotic activity in schizophrenia. However, its metabolite, EMD 59983, binds also to D(2) and D(3) dopamine (DA) receptors.
  
  
  OBJECTIVE
  The aim of this study was to test, using single photon emission computed tomography (SPECT) and [(123)I]iodobenzamide (IBZM) as the radiotracer, 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 neuroleptics was observed in all patients treated with EMD 57445.
  
  
  CONCLUSIONS
  Our results suggest that a possible antipsychotic activity of EMD 57445 in schizophrenia is not necessarily attributable to its affinity for sigma receptors, but could be simply due to the potent antidopaminergic effects of EMD 59983, its main metabolite.
authors.affiliation: Department of Psychiatry, University of Mainz, Untere Zahlbacher Strasse 8, D-55131 Mainz, Germany, gruender@mail.uni-mainz.de
authors.forename: G
authors.initials: G
authors.lastname: Gründer
authors.forename: M J
authors.initials: MJ
authors.lastname: Müller
authors.forename: J
authors.initials: J
authors.lastname: Andreas
authors.forename: N
authors.initials: N
authors.lastname: Heydari
authors.forename: H
authors.initials: H
authors.lastname: Wetzel
authors.forename: R
authors.initials: R
authors.lastname: Schlösser
authors.forename: S
authors.initials: S
authors.lastname: Schlegel
authors.forename: O
authors.initials: O
authors.lastname: Nickel
authors.forename: D
authors.initials: D
authors.lastname: Eissner
authors.forename: O
authors.initials: O
authors.lastname: Benkert
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000378:metabolism*; D001549:Benzamides / Q000378:metabolism; D001812:Blood-Brain Barrier; D003342:Corpus Striatum / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010080:Oxazoles / Q000378:metabolism* / Q000494:pharmacology; D010880:Piperidines / Q000378:metabolism* / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D011759:Pyrrolidines / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D017480:Receptors, sigma / Q000378:metabolism*; D012559:Schizophrenia / Q000188:drug therapy; D015899:Tomography, Emission-Computed, Single-Photon
chemical_list: D014150:Antipsychotic Agents; D001549:Benzamides; D010080:Oxazoles; D010880:Piperidines; D011743:Pyrimidines; D011759:Pyrrolidines; D017448:Receptors, Dopamine D2; D017480:Receptors, sigma; C103849:panamesine; C050408:alpha-(4-fluorophenyl)-4-(5-fluoro-2-pyrimidinyl)-1-piperazine butanol; C055743:3-iodo-2-hydroxy-6-methoxy-N-((1-ethyl-2-pyrrolidinyl)methyl)benzamide