14 research outputs found
Tandem Hydroformylation/Fischer Indole Synthesis: A Novel and Convenient Approach to Indoles from Olefins
The novel selective PDE9 inhibitor BAY 73-6691 improves learning and memory in rodents.
The present study investigated the putative pro-cognitive effects of the novel selective PDE9 inhibitor BAY 73-6691. The effects on basal synaptic transmission and long-term potentiation (LTP) were investigated in rat hippocampal slices. Pro-cognitive effects were assessed in a series of learning and memory tasks using rodents as subjects. BAY 73-6691 had no effect on basal synaptic transmission in hippocampal slices prepared from young adult (7- to 8-week-old) Wistar rats. A dose of 10 mu M, but not 30 mu M BAY 73-6691 enhanced early LTP after weak tetanic stimulation. The dose effective in young adult Wistar rats did not affect LTP in hippocampal slices prepared from young (7- to 8-week-old) Fischer 344 X Brown Norway (FBNF1) rats, probably reflecting strain differences. However, it increased basal synaptic transmission and enhanced early LTP after weak tetanic stimulation in hippocampal slices prepared from very old (31 - to 35-month-old) FBNF1 rats. BAY 73-6691 enhanced acquisition, consolidation, and retention of long-term memory (LTM) in a social recognition task and tended to enhance LTM in an object recognition task. Bay 73-6691 attenuated the scoplamine-induced retention deficit in a passive avoidance task, and the MK-801-induced short-term memory deficits in a T-maze alternation task. The mechanism of action, possibly through modulation of the NO/cGMP-PKG/CREB pathway, is discussed. Our findings support the notion that PDE9 inhibition may be a novel target for treating memory deficits that are associated with aging and neurodegenerative disorders such as Alzheimer's disease
Desymmetrization of 4-Dimethylsiloxy-1,6-heptadiynes through Sequential Double Silylformylation
Microwave-Assisted Protection of Primary Amines as 2,5-Dimethylpyrroles and Their Orthogonal Deprotection
Advances in understanding the renin-angiotensin-aldosterone system (RAAS) in blood pressure control and recent pivotal trials of RAAS blockade in heart failure and diabetic nephropathy
Tandem Reaction Sequences under Hydroformylation Conditions: New Synthetic Applications of Transition Metal Catalysis
Binding Free Energy Calculations for Lead Optimization: Assessment of Their Accuracy in an Industrial Drug Design Context
Finerenone: a New Mineralocorticoid Receptor Antagonist Without Hyperkalemia: an Opportunity in Patients with CKD?
Global cardiovascular protection in chronic kidney disease.
The development and progression of cardiovascular disease (CVD) and renal disorders are very closely related. In patients with chronic kidney disease (CKD), therapies proven to protect the cardiovascular and renal systems simultaneously are generally used only at low doses or not at all. In particular, patients with CKD who receive angiotensin-converting-enzyme inhibitors, angiotensin-receptor blockers, or mineralocorticoid-receptor antagonists (MRAs) often do not experience complete blockade of the renin-angiotensin-aldosterone system, primarily owing to the risk of hyperkalaemia. In this Review, we provide an overview of the available treatments required for adequate cardiorenal protection in patients with CKD. Drugs such as ÎČ-blockers that interfere with renin secretion will be discussed, in addition to agents that can prevent hyperkalaemia, such as potassium binders and nonsteroidal MRAs. Furthermore, the current literature on the role of statins, in addition to new compounds and dosing recommendations for the treatment of patients with CKD will also be reviewed. Further studies with these new compounds and doses are needed to ascertain whether these approaches can improve the long-term cardiovascular and renal prognosis in patients with CKD