Disease relevance of Web 1881FU

• Effects of delayed treatment with nebracetam on neurotransmitters in brain regions after microsphere embolism in rats [1].
• WEB 1881 FU ameliorates impairment of working memory induced by scopolamine and cerebral ischemia in the three-panel runway task [2].
• WEB 1881 FU at 32 and 56 mg/kg, administered p.o. immediately after blood flow recirculation and again 1 hr before the runway test, conducted 24 hr after ischemia, significantly reduced the increase in errors expected to occur after 5 min of ischemia [2].
• WEB 1881 FU at 10(-6) M or idebenone at 10(-6) M significantly protected against impairment of the striatal responses under the conditions of hypoglycemia [3].
• In light of these observations, the possibility that WEB 1881 FU and idebenone exert neuroprotective actions against hypoglycemic/hypoxic brain injury by activating energy metabolism with different mechanisms from each other has to be considered [3].

High impact information on Web 1881FU

• Increase of acetylcholine release by nebracetam in dog cardiac sympathetic ganglion [4].
• Acetylcholine release from the isolated ganglia by preganglionic stimulation (5 Hz) was enhanced in the presence of nebracetam, 10(-7) to 10(-5) M [4].
• The effects of nebracetam (4-aminomethyl-1-benzylpyrrolidine-2-one hemifumarate, WEB 1881FU), a potential cognitive enhancer, on acetylcholine release from the preganglionic nerve terminals were investigated in the isolated dog stellate ganglia [4].
• Histological evidence for neuroprotective action of nebracetam on ischemic neuronal injury in the hippocampus of stroke-prone spontaneously hypertensive rats [5].
• These findings suggest that in cultured cerebellar granule cells, nebracetam attenuates the external Ca2+ influx derived from the activation of N-methyl-D-aspartate receptor-gated rather than voltage-gated Ca2+ channels [6].

Chemical compound and disease context of Web 1881FU

• In addition, nebracetam and pentobarbital relatively recovered the increase of 2DG uptake in the hippocampus under hypoxia for 45 min [7].
• The present result suggests that nebracetam and pentobarbital exert neuroprotective actions against not only ischemia but also glutamate toxicity [7].

Biological context of Web 1881FU

• Effects of a cholinergic nootropic (WEB 1881 FU) on event-related potentials recorded in incidental and intentional memory tasks [8].
• These findings further support the notion that nebracetam protects against ischemic delayed neuronal cell death in the hippocampus [5].
• From these results, WEB 1881 FU seems to act on M1-mACh receptors, and its long-term administration probably induces the down-regulation of mACh receptors, mainly M1-mACh receptors in the hippocampus and striatum and M2-mACh receptors in the cerebellum [9].
• Nebracetam (50 and 100 mg/kg), given orally 10 min after reperfusion, dose-dependently protected against ischemic delayed neuronal damage in the SHRSP with occlusion; however, the blood pressure remained unchanged following nebracetam administration [5].
• After nebracetam, the frequency-response curves of heart rate for preganglionic stellate stimulation (0.25-4 Hz) were not altered in the untreated and atropine-pretreated animals, but the curves (2.5-40 Hz) were shifted to the left in the hexamethonium-pretreated animals [10].

Anatomical context of Web 1881FU

• The WEB 1881 FU-competition curve for [3H]pirenzepine binding in hippocampal membranes was rightward-shifted by GTP gamma S; such behavior was also observed in the case of oxotremorine but not with scopolamine [9].
• The protective effect of nebracetam on ischemic neuronal damage was histologically examined in the pyramidal cell layer of the hippocampal CA1 subfield 7 days after operation using stroke-prone spontaneously hypertensive rats (SHRSP) subjected to 10-min bilateral carotid occlusion [5].
• The astrocytes treated with nebracetam showed a decrease in 3H-valine incorporation [11].
• The ganglionic stimulants were given directly into the cardiac sympathetic ganglia through the right subclavian artery (i.a.). Nebracetam, 5 mg/kg, i.v. caused a slight and temporal increase in heart rate [10].
• Effect of nebracetam on nicotinic and muscarinic acetylcholine receptors expressed in Xenopus oocyte by injecting exogenous mRNA [12].

Associations of Web 1881FU with other chemical compounds

• Effects of 4-aminomethyl-1-benzylpyrrolidin-2-one-hemifumarate (WEB 1881 FU), a novel pyrrolidinone nootropic, on acetylcholine (ACh) receptors and adrenoceptors were investigated using crude membranes of the rat brain [9].
• Effect of nebracetam on content of high-energy phosphates and morphometry of rat astrocytes in vitro. Comparison with piracetam [11].
• Cultured astrocytes treated with either nebracetam or piracetam showed decreased intracellular ATP and PCr levels [11].
• Furthermore, nebracetam failed to affect dose-dependent post-ganglionic stimulation by McN-A-343 (1-32 micrograms), 1,1-dimethyl-4-phenylpiperazinium (1-32 micrograms) and angiotensin II (0.1 and 0.2 micrograms) administered i.a. directly to the ganglia [10].

Gene context of Web 1881FU

• Therefore, nebracetam seems to produce a neuroprotective action by interacting, at least in part, with NMDA receptor-operated Ca2+ channels [13].
• Evaluation of the neuroprotective action of WEB 1881 FU on hypoglycemia/hypoxia-induced neuronal damage using rat striatal slices [3].

Analytical, diagnostic and therapeutic context of Web 1881FU

• 1. The effects of delayed treatment with nebracetam, a novel nootropic drug, on neurotransmitters of brain regions were examined in rats with microsphere embolism-induced cerebral ischaemia [1].
• The ineffectiveness of nebracetam in the in vivo microdialysis may be due to low levels of the concentration of nebracetam when the agent was administered i.p. at a dose of 30 mg/kg, since the brain blood concentration of this agent is pharmacokinetically estimated to be no more than 15 microM when this dose of nebracetam is employed [14].

References