Effects of dizocilpine, midazolam and their co-application on the trimethyltin (TMT)-induced rat model of neurodegeneration

The aim of this study was to explore the effect of NMDA receptor antagonist dizocilpine (MK-801) and GABAA receptor potentiator midazolam on the cognitive deficit and hippocampal cell loss induced by TMT and to investigate whether their co-application is associated with enhanced neuroprotective effects. Co-application of MK-801 and midazolam provided mild neuroprotective effect with respect to the histological parameters, while the compounds alone were largely ineffective. All three neuroprotective treatments induced similar degree of therapeutic effect in Morris water maze.THIS DATASET IS ARCHIVED AT DANS/EASY, BUT NOT ACCESSIBLE HERE. TO VIEW A LIST OF FILES AND ACCESS THE FILES IN THIS DATASET CLICK ON THE DOI-LINK ABOV

Data for: Synthetic Structural Modifications of Neurosteroid Pregnanolone Sulfate: Assessment of Neuroprotective Effects In Vivo

The effect of neuroactive steroids on rodent behaviorTHIS DATASET IS ARCHIVED AT DANS/EASY, BUT NOT ACCESSIBLE HERE. TO VIEW A LIST OF FILES AND ACCESS THE FILES IN THIS DATASET CLICK ON THE DOI-LINK ABOV

Novel tacrine-tryptophan hybrids: Multi-target directed ligands as potential treatment for Alzheimer's disease

A combination of tacrine and tryptophan led to the development of a new family of heterodimers as multi-target agents with potential to treat Alzheimer's disease. Based on the in vitro biological profile, compound S-K1035 was found to be the most potent inhibitor of human acetylcholinesterase (hAChE) and human butyrylcholinesterase (hBChE), demonstrating balanced IC50 values of 6.3 and 9.1 nM, respectively. For all the tacrine-tryptophan heterodimers, favorable inhibitory effect on hAChE as well as on hBChE was coined to the optimal spacer length ranging from five to eight carbon atoms between these two pharmacophores. S-K1035 also showed good ability to inhibit A\u3b242 self-aggregation (58.6 \ub1 5.1% at 50 \u3bcM) as well as hAChE-induced A\u3b240 aggregation (48.3 \ub1 6.3% at 100 \u3bcM). The X-ray crystallographic analysis of TcAChE in complex with S-K1035 pinpointed the utility of the hybridization strategy applied and the structures determined with the two K1035 enantiomers in complex with hBChE could explain the higher inhibition potency of S-K1035. Other in vitro evaluations predicted the ability of S-K1035 to cross blood-brain barrier and to exert a moderate inhibition potency against neuronal nitric oxide synthase. Based on the initial promising biochemical data and a safer in vivo toxicity compared to tacrine, S-K1035 was administered to scopolamine-treated rats being able to dose-dependently revert amnesia