PMID- 16983399
OWN - NLM
STAT- MEDLINE
DCOM- 20070927
LR  - 20181201
IS  - 1470-269X (Print)
IS  - 1470-269X (Linking)
VI  - 7
IP  - 4
DP  - 2007 Aug
TI  - No evidence for binding of clozapine, olanzapine and/or haloperidol to selected 
      receptors involved in body weight regulation.
PG  - 275-81
AB  - The underlying mechanisms of antipsychotic (AP)-induced weight gain are unknown, 
      but both central and peripheral AP target receptors could potentially be 
      involved. This study used radioligand binding assays to compare the binding 
      affinities of clozapine, olanzapine and haloperidol for candidate receptors 
      potentially involved in AP-induced weight gain. Selected candidates derived from 
      known pathways involved in body weight regulation included receptors classified 
      as anorexigenic (bombesin receptor subtype 3, calcitonin gene-related peptide 
      receptor, cholecystokinin receptor, melanocortin-4 receptor, neurotensin receptor 
      1) or orexigenic (cannabinoid receptor 1, galanin 1 receptor, 
      melanin-concentrating hormone receptor (MCHR), neuropeptide Y1 receptor) as well 
      as receptors involved in physiological actions related to digestion and fluid 
      homeostasis (angiotensin II type 1 receptor, bradykinin B2 receptor, endothelin 
      receptor, neurokinin 1 receptor, vasoactive intestinal polypeptide receptor 1). 
      Clozapine, olanzapine and haloperidol exhibited negligible affinities to all of 
      these receptors except for the MCHR (Ki=501 nM; haloperidol). With respect to 
      other candidates from (neuro)transmitter systems already suggested to be involved 
      in AP-induced weight gain, the binding profile of olanzapine resembled that of 
      clozapine, with high affinity (Ki<10 nM) for serotonin (5-HT) 5-HT2A, 5-HT2C and 
      5-HT6, muscarinic M1 and histamine H1 receptors. In contrast, the binding profile 
      of haloperidol was substantially different (high affinity only for the dopamine 
      D1 receptor). In conclusion, we have not identified a novel binding site of the 
      two investigated atypical AP that could contribute to the induced weight gain.
FAU - Theisen, F M
AU  - Theisen FM
AD  - Clinical Research Group, Department of Child and Adolescent Psychiatry, 
      University of Marburg, Marburg, Germany. frank.theisen@med.uni-marburg.de
FAU - Haberhausen, M
AU  - Haberhausen M
FAU - Firnges, M A
AU  - Firnges MA
FAU - Gregory, P
AU  - Gregory P
FAU - Reinders, J H
AU  - Reinders JH
FAU - Remschmidt, H
AU  - Remschmidt H
FAU - Hebebrand, J
AU  - Hebebrand J
FAU - Antel, J
AU  - Antel J
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20060919
PL  - United States
TA  - Pharmacogenomics J
JT  - The pharmacogenomics journal
JID - 101083949
RN  - 0 (Antipsychotic Agents)
RN  - 0 (Receptors, Cell Surface)
RN  - 12794-10-4 (Benzodiazepines)
RN  - J60AR2IKIC (Clozapine)
RN  - J6292F8L3D (Haloperidol)
RN  - N7U69T4SZR (Olanzapine)
SB  - IM
MH  - Animals
MH  - Antipsychotic Agents/*metabolism/pharmacology
MH  - Benzodiazepines/metabolism/pharmacology
MH  - Body Weight/*drug effects
MH  - Clozapine/*metabolism/pharmacology
MH  - Haloperidol/*metabolism/pharmacology
MH  - Humans
MH  - Olanzapine
MH  - Protein Binding
MH  - Radioligand Assay
MH  - Receptors, Cell Surface/*metabolism
EDAT- 2006/09/20 09:00
MHDA- 2007/09/28 09:00
CRDT- 2006/09/20 09:00
PHST- 2006/09/20 09:00 [pubmed]
PHST- 2007/09/28 09:00 [medline]
PHST- 2006/09/20 09:00 [entrez]
AID - 6500418 [pii]
AID - 10.1038/sj.tpj.6500418 [doi]
PST - ppublish
SO  - Pharmacogenomics J. 2007 Aug;7(4):275-81. doi: 10.1038/sj.tpj.6500418. Epub 2006 
      Sep 19.