MRZ-99030 - A novel modulator of Aβ aggregation: II - Reversal of Aβ oligomer-induced deficits in long-term potentiation (LTP) and cognitive performance in rats and mice.

β-amyloid1-42 (Aβ1-42) is a major endogenous pathogen underlying the aetiology of Alzheimer's disease (AD). Recent evidence indicates that soluble Aβ oligomers, rather than plaques, are the major cause of synaptic dysfunction and neurodegeneration. Small molecules that suppress Aβ aggregation, reduce oligomer stability or promote off-pathway non-toxic oligomerization represent a promising alternative strategy for neuroprotection in AD.

GW406381, a novel COX-2 inhibitor, attenuates spontaneous ectopic discharge in sural nerves of rats following chronic constriction injury.

There are several lines of evidence to suggest that cyclooxygenase-2 (COX-2) plays an important role in the generation and maintenance of neuropathic pain states following peripheral nerve injury. However, COX-2 inhibitors are generally ineffective in reversing mechanical allodynia and hyperalgesia in models of neuropathic hypersensitivity. Here, we have investigated the effects of GW406381, a novel COX-2 inhibitor, on mechanical allodynia, hyperalgesia and generation of spontaneous ectopic discharge in rats following chronic constriction injury (CCI) of the sciatic nerve and compared it with rofecoxib.