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In vivo receptor occupancy method that simultaneously quantifies four tracers: raclopride, pirenzepine, MDL‐100907, and SB‐221284
Author(s) -
Schmelzer Kara,
Craig Darren,
Bonhaus Doug W,
Tabatabaei Ali
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1127.15
Subject(s) - raclopride , pirenzepine , in vivo , pharmacology , chemistry , serotonin , receptor , 5 ht receptor , dopamine receptor d2 , antipsychotic , muscarinic acetylcholine receptor , dopamine receptor , biology , medicine , biochemistry , schizophrenia (object oriented programming) , microbiology and biotechnology , psychiatry
The atypical antipsychotics share the common attributes of working on serotonin and dopamine receptors. However, a comprehensive mechanism of action of these agents is unknown. In order to better elucidate the mechanism by which these drugs produce their therapeutic and the undesired effects, a robust method for measuring in vivo receptor binding is needed. The authors developed a liquid chromatography/triple quad mass spectral detectors (LC/MS/MS) method to measure the brain distribution of receptor occupancy using tracers targeting dopamine D 2 , serotonin 5‐HT 2A , 5‐HT 2C and muscarinic M 1 receptors. The tracers are raclopride, MDL‐100907, SB‐221284 and pirenzepine, respectively. All four non‐radiolabeled tracers were detectable in discrete rat brain areas after intravenous administration. These tracers demonstrated a differential brain distribution corresponding to the regional differences in their respective receptor densities. Oral pretreatment of various antipsychotic agents that occupy these receptors decreased this differential distribution in a dose‐dependent manner. Our results demonstrate the utility of LC/MS/MS to quantify the in vivo receptor occupancy of antipsychotic and other agents acting in the CNS.