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The affinities of olanzapine, clozapine, haloperidol, and four potential antipsychotics were compared on binding to the neuronal receptors of a number of neurotransmitters. In both rat tissues and cell lines transfected with human receptors olanzapine had high affinity for dopamine D1, D2, D4, serotonin (5HT)2A, 5HT2C, 5HT3, alpha 1-adrenergic, histamine(More)
According to the amyloid cascade hypothesis, cerebral deposition of amyloid-β peptide (Aβ) is critical for Alzheimer's disease (AD) pathogenesis. Aβ generation is initiated when β-secretase (BACE1) cleaves the amyloid precursor protein. For more than a decade, BACE1 has been a prime target for designing drugs to prevent or treat AD. However, development of(More)
Functional gamma-secretase inhibitors (FGSIs) can block the cleavage of several transmembrane proteins including amyloid precursor protein (APP), and the cell fate regulator Notch-1. FGSIs, by inhibiting APP processing, block the generation of amyloid beta (Abeta) peptides and may slow the development of Alzheimer's disease. FGSIs used to inhibit APP(More)
A high affinity (KD 35 nM) binding site for [3H]cocaine is detected in rat brain striatum present at 2-3 pmol/mg protein of synaptic membranes. This binding is displaced by cocaine analogues with the same rank order as their inhibition of [3H]dopamine ([3H]DA) uptake into striatal synaptosomes (r = 0.99), paralleling the order of their central stimulant(More)
Xanomeline [3(3-hexyloxy-1,2,5-thiadiazol-4-yl)-1,2,5,6-tetrahydro-1- methylpyridine] has been evaluated as a muscarinic receptor agonist. In vitro, xanomeline had high affinity for muscarinic receptors in brain homogenates, but had substantially less or no affinity for a number of other neurotransmitter receptors and uptake sites. In cells stably(More)
High-affinity binding sites for [3H]cocaine (levo-[benzoyl-3,4-3H(N)]) were detected in membrane preparations from rat brain and liver. Analysis of binding to rat whole brain membranes revealed a high-affinity site (Kd = 16 nM) present at 0.65 pmol/mg of protein and a lower affinity site of (Kd = 660 nM) present at 5.1 pmol/mg of protein. The striatum had a(More)
The interactions of the atypical antipsychotic drugs (APD) clozapine, olanzapine, risperidone, quetiapine and ziprasidone with muscarinic receptors were reviewed. Only clozapine and olanzapine have marked affinity for muscarinic receptors in radioligand binding studies; however, the affinity of these compounds is considerably lower than classical muscarinic(More)
Olanzapine, an atypical antipsychotic, has a broad receptor binding profile, which may account for its pharmacological effects in schizophrenia. In vitro receptor binding studies showed a high affinity for dopamine D2, D3, and D4 receptors; all 5-HT2 receptor subtypes and the 5-HT6 receptor; muscarinic receptors, especially the M1 subtype: and alpha(More)
Group II metabotropic glutamate (mGlu) receptor agonists, including (1S,2S,5R,6S)-2-aminobicyclo[3.1.0]hexane-2,6-dicarboxylate monohydrate (LY354740) and (-)-2-oxa-4-aminobicyclo[3.1.0]hexane-4,6-dicarboxylate (LY379268), have demonstrated efficacy in animal models of anxiety and schizophrenia, and LY354740 decreased anxiety in human subjects. Herein, we(More)
Activation of muscarinic m1 receptors which are coupled to the phosphoinositide (PI) second messenger transduction system is the initial objective of cholinergic replacement therapy in Alzheimer's disease. Thus, we evaluated the ability of the selective muscarinic receptor agonist (SMRA) xanomeline to stimulate in vivo phosphoinositide (PI) hydrolysis and(More)