If proven, the apparent lack of D2R blockade by alstonine would represent an innovative pharmacodynamic basis for antipsychotic properties.
The data obtained in this study corroborate our previous hypothesis that alstonine does not bind to D2R because the QAR data clearly demonstrate that alstonine does not bind to D2R.
There are approximately 40 different antipsychotics on the market, all of which block D2R to some extent (Insel 2010; Ellenbroek 2012).
Neurochemical studies of the brains of patients with liver disease have confirmed for the most part the results from neuroimaging studies: a significant decrease in D2R levels in the basal ganglia and no observed decrease in dopamine levels (Table 1).
Liver disease Loss of D2R in GP 1995 Mousseau et al.
DAT/autorad (normal) 2008 D2R/autorad (normal) D1R/autorad (normal) CB1/autorad (normal) TH/immunohistochemistry (normal) DA-HVA/HPLC (normal) Abbreviations: autorad, autoradiography; CB1, cannabinoid receptor 1; ChAT, choline acetyltransferase; DA, dopamine; DAR, dopamine release; DOPAC, 3,4-dihydroxyphenylacetic acid; D2R, dopamine receptor; FDG, fluorodeoxyglucose; GABAaR, [gamma]-aminobutyric acid A receptor; GAD, glutamic acid decarboxylase; GP, globus pallidus; im, intramuscular; iv, intravenous; mAChR, muscarinic acetylcholine receptor; MRS, magnetic resonance spectroscopy; ND, not determined; IME, norepinephrine; sc, subcutaneous; SN, substantia nigra; SNpr, substantia nigra pars reticulata; TH, tyrosine hydroxylase.
5 mg Mn/kg body weight; range, 152-174 mg Mn/kg body weight) on DAT or D2R receptor levels using autoradiography or tyrosine hydroxylase immunohistochemistry, or on the concentration of dopamine and its metabolite homovanillic acid (HVA) measured by HPLC with electrochemical detection in the caudate or putamen, relative to naive controls (Guilarte et al.
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