The Novel Selective PDE9 Inhibitor BAY 73-6691 Improves Learning and Memory in Rodents

F Josef van der Staay, Kris Rutten, Lars Bärfacker, Jean Devry, Christina Erb, Heike Heckroth, Dagmar Karthaus, Adrian Tersteegen, Marja van Kampen, Arjan Blokland, Jos Prickaerts, Klaus G Reymann, Ulrich H Schröder, etc.

Neuropharmacology. 2008 Oct;55(5):908-18.

PMID: 18674549

Abstract:

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 microM, but not 30 microM, 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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP794568926	BAY 73-6691		794568-92-6	Price