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3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase inhibitors, or statins, reduce the incidence of strokes and reduce infarct volume after cerebral ischemia in mice. Excitoxicity caused by overstimulation of glutamate receptors is a major cause of neuronal death after an ischemic brain insult. Experiments presented here explored whether statins protect(More)
  • Joseph Milano, Jenny Mckay, Claude Dagenais, Linda Foster-Brown, Francois Pognan, Reto Gadient +4 others
  • 2004
Running title:-Secretase inhibitors cause intestinal goblet cell metaplasia and the induction of the transcriptional activator of differentiation Rath1 ABSTRACT It is anticipated that-secretase inhibitors (-Sec-I) which modulate Notch processing will alter differentiation in tissues whose architecture is governed by Notch signaling. To explore this(More)
It is anticipated that gamma-secretase inhibitors (gamma-Sec-I) that modulate Notch processing will alter differentiation in tissues whose architecture is governed by Notch signaling. To explore this hypothesis, Han Wistar rats were dosed for up to 5 days with 10-100 micromol/kg b.i.d. gamma-Sec-I from three chemical series that inhibit Notch processing in(More)
The limbic system-associated membrane protein (LAMP) is a cell surface glycoprotein expressed by cortical and subcortical regions of the mammalian CNS that comprise or receive direct projections from limbic system structures. The early and restricted expression of LAMP has led to its postulated role in neural development. Purification and biochemical(More)
The κ-opioid receptor plays a central role in mediating the response to stressful life events. Inhibiting κ-opioid receptor signaling is proposed as a mechanism for treating stress-related conditions such as depression and anxiety. Preclinical testing consistently confirms that disruption of κ-opioid signaling is efficacious in animal models of mood(More)
BACKGROUND AND PURPOSE Quetiapine has a range of clinical activity distinct from other atypical antipsychotic drugs, demonstrating efficacy as monotherapy in bipolar depression, major depressive disorder and generalized anxiety disorder. The neuropharmacological mechanisms underlying this clinical profile are not completely understood; however, the major(More)
Humans and higher primates are unique in that they lack uricase, the enzyme capable of oxidizing uric acid. As a consequence of this enzyme deficiency, humans have high serum uric acid levels. In some people, uric acid levels rise above the solubility limit resulting in crystallization in joints, acute inflammation in response to those crystals causes(More)
Herein, we describe the discovery of inhibitors of norepinephrine (NET) and dopamine (DAT) transporters with reduced activity relative to serotonin transporters (SERT). Two compounds, 8b and 21a, along with nomifensine were tested in a rodent receptor occupancy study and demonstrated dose-dependent displacement of radiolabeled NET and DAT ligands. These(More)
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