Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.1.7 (acetylcholinesterase)
 28,390 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A number of studies indicate that free radicals are involved in the neurodegeneration in Alzheimer's disease (AD). The present study was mainly conducted to examine the effect of Huperzine B on H(2)O(2) induced toxicity in rat pheochromocytoma line PC12 by measuring cell lesion, level of lipid peroxidation and antioxidant enzyme activities. Following a 30 min exposure of the cells to H(2)O(2) (150 microM), a marked decrease in cell survival, activities of glutathione peroxidase and catalase as well as increased production of malondialdehyde (MDA) were found. Pretreatment of the cells with huperzine B (10-100 microM) prior to H(2)O(2) exposure significantly elevated the cell survival, antioxidant enzyme activities and decreased the level of MDA. The above-mentioned neuroprotective effects are also observed with tacrine (1 microM), donepezil (10 microM) and galanthamine (10 microM), suggesting that the neuroprotective effects of cholinesterase inhibitor might partly contribute to the clinical efficacy in AD treatment.
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PMID:Huperzine B, a novel acetylcholinesterase inhibitor, attenuates hydrogen peroxide induced injury in PC12 cells. 1099 45

ZT-1 has been developed as a novel acetylcholinesterase inhibitor, but is rapidly degraded to huperzine A (Hup A) in water or aqueous organic solvents. A sensitive method has been developed for simultaneous determination of ZT-1 and its active metabolite Hup A in blood, and was applied to the investigation of the pharmacokinetics of ZT-1 in rats. The method involves immediate hydrogenation of ZT-1 with sodium borohydride to the stable form rZT-1 following blood sampling. The NaBH4-treated blood sample is then submitted to liquid-liquid extraction, and the resultant extract is analyzed by liquid chromatography with electrospray ionization and tandem mass spectrometry. Huperzine B is used as internal standard for the quantification. ZT-1 was found to be rapidly absorbed in the intestinal tract, with a time to reach the peak blood concentration (Tpeak) of 5 min after an intragastric dose of ZT-1 embedded in povidone to rats at 0.5 mg ZT-1/kg. The mean maximum blood concentration (Cmax) and area under the blood level-time curve (AUC(0 --> 8)) of ZT-1 were 1.57 ng/mL and 0.48 ng. h/mL, respectively. The Tpeak, Cmax, and AUC values of the metabolite Hup A were 0.22 h, 109.9 ng/mL, and 96.3 ng. h/mL, respectively. Following an intravenous dose of 0.1 mg ZT-1/kg rat body weight, the blood concentration of ZT-1 was higher than that of Hup A, and the AUC(0 --> 8) values were 26.2 ng. h/mL for ZT-1 and 6.0 ng. h/mL for Hup A. The elimination half-lives (T1/2) of ZT-1 and Hup A were 0.68 and 1.47 h, respectively. The oral bioavailability (F) of intact ZT-1 in rats treated with ZT-1 embedded in povidone was very low, 0.37%.
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PMID:A sensitive method for the determination of the novel cholinesterase inhibitor ZT-1 and its active metabolite huperzine A in rat blood using liquid chromatography/tandem mass spectrometry. 1505 75