| Item type: | Article | ||||
|---|---|---|---|---|---|
| Journal or Publication Title: | Neuropharmacology | ||||
| Publisher: | PERGAMON-ELSEVIER SCIENCE LTD | ||||
| Place of Publication: | OXFORD | ||||
| Volume: | 109 | ||||
| Page Range: | pp. 1-6 | ||||
| Date: | 2016 | ||||
| Institutions: | Medicine > Lehrstuhl für Anästhesiologie | ||||
| Identification Number: |
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| Keywords: | CHOLINESTERASE-INHIBITORS; BLOOD CHOLINESTERASE; ALZHEIMERS-DISEASE; RAT-BRAIN; ACETYLCHOLINESTERASE; PHARMACOKINETICS; INFLAMMATION; METABOLISM; PARAMETERS; SURVIVAL; Butyrylcholinesterase; Acetylcholinesterase; Alzheimer's disease; Physostigmine; Neostigmine; Inflammatory disease; Rat; Ellman's reagent; Cholinesterase inhibitors | ||||
| Dewey Decimal Classification: | 600 Technology > 610 Medical sciences Medicine | ||||
| Status: | Published | ||||
| Refereed: | Yes, this version has been refereed | ||||
| Created at the University of Regensburg: | Yes | ||||
| Item ID: | 42401 |
Web of ScienceAbstract
Previous and more recent studies show that cholinesterase inhibitors (ChE-Is) are an important possibility for therapeutic intervention in Alzheimer's Disease, sepsis and other inflammatory syndromes. ChE-Is maintain high levels of acetylcholine (ACh) determining beneficial effects on the disease process. Despite numerous efforts to identify the appropriate choice of agents and dose of ChE-Is, a ...
Abstract
Previous and more recent studies show that cholinesterase inhibitors (ChE-Is) are an important possibility for therapeutic intervention in Alzheimer's Disease, sepsis and other inflammatory syndromes. ChE-Is maintain high levels of acetylcholine (ACh) determining beneficial effects on the disease process. Despite numerous efforts to identify the appropriate choice of agents and dose of ChE-Is, a common protocol regarding concentration- and species-dependent differences in inhibitory potency (IC 50) of clinical relevant ChE-Is is still not available. To evaluate the in vitro sensitivity of Acetyl- and Butyrylcholinesterase (AChE, BChE), we compared the concentration-response effects of physostigmine and neostigmine on cholinesterases in whole blood from rat and human. A spectrophotometrical test system based on in vitro Ellman's reagent has been used to determine the kinetic properties of clinical relevant ChE-Is. In vitro, the enzyme activity of human AChE and BChE was inhibited in a concentration-dependent manner until a residual activity of 4-6% for AChE and 20-30% for BChE (IC 50 human AChE: 0.117 +/- 0.007 mu M physostigmine, 0.062 +/- 0.003 mu M neostigmine; IC 50 human BChE: 0373 +/- 0.089 mu M neostigmine; 0.059 +/- 0.012 mu M physostigmine). The inhibition curve of rat BChE in contrast showed no concentration-dependency for physostigmine and neostigmine (87% residual activity even at high inhibitor concentrations). Rat AChE was inhibited in a concentration-dependent manner until a residual activity of 53%. The results suggest that cholinesterases from human and rat show marked species- and inhibitor dependent differences in sensitivity to physostigmine and neostigmine. Knowledge of such differences may be critical in assessing the possible therapeutic effects of ChE-Is in both species and may guide researchers in the optimal design of future experiments regarding the application of ChE-Is. (C) 2016 Elsevier Ltd. All rights reserved.
Metadata last modified: 17 Mar 2020 11:28
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