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Aripiprazole is the first next-generation atypical antipsychotic with a mechanism of action that differs from currently marketed typical and atypical antipsychotics. Aripiprazole displays properties of an agonist and antagonist in animal models of dopaminergic hypoactivity and hyperactivity, respectively. This study examined the interactions of aripiprazole(More)
BACKGROUND Aripiprazole (7-{4-[4-(2,3-dichlorophenyl)-1-piperazinyl]butoxy}-3,4-dihydro-2(1H)-quinolinone) is a novel antipsychotic with a mechanism of action that differs from current typical and atypical antipsychotics. Aripiprazole interacts with a range of receptors, including serotonin [5-hydroxytryptamine (5-HT)] and dopamine receptors. MATERIALS(More)
The goal of this study was to develop and validate ex vivo binding assays for serotonin (SERT), norepinephrine (NET) and dopamine (DAT) transporters, and to use these assays to evaluate the binding site occupancy of triple and double monoamine reuptake inhibitors in rat brains. This study demonstrated that while autoradiographic methods provided anatomic(More)
Phosphodiesterase 10A (PDE10A) inhibitors increase the functionality of striatal medium spiny neurons and produce antipsychotic-like effects in rodents by blocking PDE10A mediated hydrolysis of cAMP and/or cGMP. In the current study, we characterized a radiolabeled PDE10A inhibitor, [(3)H]BMS-843496, and developed an ex vivo PDE10 binding autoradiographic(More)
BMS-505130 is a potent and selective serotonin transport inhibitor; K(i) for binding to the serotonin transporter = 0.18 nM (K(i) values for binding to the norepinephrine and dopamine transporters = 4.6 and 2.1 microM, respectively). In platelet serotonin uptake studies BMS-505130 (5 mg/kg, p.o.) produced a robust inhibition of serotonin uptake. In(More)
The known interactions between the serotonergic and neurokinin systems suggest that serotonin reuptake inhibitor (SSRIs) efficacy may be improved by neurokinin-1 receptor (NK1R) antagonism. In the current studies combination of a subeffective dose of an SSRI (0.3 mg/kg fluoxetine or 0.03 mg/kg citalopram) with a subeffective dose of an NK1R antagonist (0.3(More)
INTRODUCTION A radioligand for measuring the density of corticotropin-releasing factor subtype-1 receptors (CRF1 receptors) in living animal and human brain with positron emission tomography (PET) would be a useful tool for neuropsychiatric investigations and the development of drugs intended to interact with this target. This study was aimed at discovery(More)
The addition of the calcium ionophore A23187 to rabbit neutrophils increases the amount of actin associated with the cytoskeleton regardless of the presence or absence of calcium in the incubation medium. In the presence of extracellular calcium, the effect of A23187 is biphasic with respect to concentration. The action of the ionophore is rapid, transient,(More)
Stimulation of rabbit neutrophils by the chemotactic factors fMet-Leu-Phe and leukotriene B4, by platelet activating factor, or by arachidonic acid produces a rapid and dose-dependent increase in the amounts of actin and of a 65,000-mol-wt protein associated with the cytoskeleton. Phorbol 12-myristate, 13-acetate, the calcium ionophore A23187 in the(More)
Kinases mediating phosphorylation and activation of cytosolic phospholipase A2 (cPLA2) in intact cells remain to be fully characterized. Platelet-activating factor stimulation of human neutrophils increases cPLA2 phosphorylation. This increase is inhibited by PD 98059, a mitogen-activated protein (MAP)/extracellular signal-regulating kinase (erk) 1(More)