Michael A Reilly

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The efficacy of gamma-secretase inhibitors in vivo has, to date, been generally assessed in transgenic mouse models expressing increased levels of amyloid-beta (Abeta) peptide thereby allowing the detection of changes in Abeta production. However, it is not clear whether the in vivo potency of gamma-secretase inhibitors is independent of the level of(More)
There is a substantial body of evidence indicating that beta-amyloid peptides (Abeta) are critical factors in the onset and development of Alzheimer's disease (AD). One strategy for combating AD is to reduce or eliminate the production of Abeta through inhibition of the gamma-secretase enzyme, which cleaves Abeta from the amyloid precursor protein (APP). We(More)
Plaques in the parenchyma of the brain containing Abeta peptides are one of the hallmarks of Alzheimer's disease. These Abeta peptides are produced by the final proteolytic cleavage of the amyloid precursor protein by the intramembraneous aspartyl protease gamma-secretase. Thus, one approach to lowering levels of Abeta has been via the inhibition of the(More)
The present study investigated the actions of cocaine and some of its metabolites and analogs upon the synaptosomal (P2) synthesis and release of dopamine appearing from [14C]phenylalanine. Also examined was the influence of reserpine upon these actions of cocaine. The P2 preparations from the rat caudate nucleus were incubated with the drugs for(More)
An apparent inverse relationship between smoking and Parkinson's disease prompted an investigation of the effect of chronic nicotine administration on dopaminergic and serotonergic receptors in rat brain. Nicotine, 0.8 mg/kg, was injected once daily, five times per week, for 6 weeks. In nucleus accumbens the Kd for [3H]domperidone was increased 2-4-fold,(More)
Observation of reduced levels of glutamic acid and aspartic acid in brain of weanling rats exposed perinatally to aspartame prompted a study of the effect of this food additive on glutamatergic receptor kinetics. Aspartame 500 mg/kg/day in drinking water was administered to Sprague-Dawley rats throughout gestation and lactation. Brain was excised from(More)
Significant positive correlation between the ligand binding values for beta-adrenergic receptors and those for muscarinic cholinergic receptors was found in five inbred strains of mice (r = 0.84) and in different vertebrate species (r = 0.99). Comparative analysis of analogous receptor studies done on various brain regions in other laboratories revealed(More)
In rat, chronic lithium treatment lowered the Kd of [3H]-mepyramine in midbrain, and reduced the Bmax in midbrain and pons-medulla. Binding of [3H]flunitrazepam in cerebellum and midbrain was not altered. The suggestion that some actions of lithium may occur by way of central nervous system receptors is further supported by these observations that lithium's(More)
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