This review is devoted to comparative pharmacological analysis of synthetic drugs such as memantine and its isomers, as well as tacrine, velnacrine, rivastigmine, and donepezil, with natural alkaloids, terpenoids, and triterpenoid peroxides, which are used to treat dementia, Alzheimer's and Parkinson's diseases, myasthenia gravis and other neurodegenerative diseases. Recently discovered by French scientists from Marseille triterpenoid hydroperoxides demonstrate high activity as potential therapeutic agents for the treatment of dementia. The information presented in this review is of great interest to pharmacologists, medical chemists, physiologists, neurologists and doctors, as well as for the pharmaceutical industry.

01 Jan 2013·Clinical Hemorheology and MicrocirculationQ4 · MEDICINE

Effects of acetylcholine on an animal model of inflammation

Q4 · MEDICINE

Article

Author: Silva-Herdade, A.S. ; Saldanha, C.

Acetylcholinesterase (AChE) is found both on the membranes of neuronal and non-neuronal cells. In this study we performed intravenous administrations of velnacrine (VLN) and acetylcholine (ACh), respectively, AChE inhibitor and substrate, in an animal model of lipopolysaccharide (LPS)-induced inflammation in Wistar rats. Using intravital microscopy the number of rolling and adherent leukocytes in post-capillary venules was monitorized and blood samples were collected for TNF-α plasma concentrations determination. Our results showed that in presence of LPS, ACh has an anti-inflammatory effect, seen by a decrease in TNF-α plasma levels and maintains the number of rolling and adherent leukocytes. The presence of VLN before LPS almost blocked the LPS-induced rolling and TNF-α releasing. Thereby VLN seems to have, like ACh, an anti-inflammatory effect by diminishing TNF-α concentrations.

01 Mar 2009·Cell Biology InternationalQ4 · BIOLOGY

Redox thiol status plays a central role in the mobilization and metabolism of nitric oxide in human red blood cells

Q4 · BIOLOGY

Article

Author: Carlota Saldanha ; Teresa Santos-Freitas ; Filomena Almeida Carvalho ; José Pedro Lopes de Almeida ; Ana Santos Silva-Herdade

AbstractWe assessed the redox thiol status influence on nitric oxide (NO) metabolism and efflux in erythrocytes stimulated with acetylcholinesterase substrate (acetylcholine, ACh) and inhibitor (velnacrine maleate, VM). Erythrocyte suspensions from healthy donors were incubated with increasing concentrations of dithiothreitol (1–50 μM), in the presence and absence of acetylcholine/velnacrine (10 μM). Levels of NO, nitrite/nitrate, S‐nitrosohemoglobin, peroxynitrite and S‐nitrosoglutathione were determined by spectrofluorimetric and spectrophotometric methods.Dithiothreitol significantly mobilized NO toward nitrite/nitrate and S‐nitrosoglutathione, and decreased the amount of NO efflux. Both ACh/VM induce changes on the levels of erythrocyte nitrite/nitrate dependent on the DTT concentration. Higher levels of peroxynitrite and S‐nitrosoglutathione were seen with velnacrine in presence of DTT 1 and 50 μM.We concluded that dithiothreitol‐induced activation of erythrocyte thiol status decreases NO efflux and allows greater intracellular NO mobilization onto different derivative molecules, both in the absence and presence of acetylcholinesterase substrate and inhibitor.

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Indication	Highest Phase	Country/Location	Organization	Date
Alzheimer Disease	NDA/BLA	US	-	-
Alzheimer Disease	NDA/BLA	GB	-	-

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