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EFFECTS OF 4-(o-BENZYLPHENOXY)-N-METHYLBUTYLAMINE HYDROCHLORIDE (BIFEMELANE) ON THE SYNTHESIS OF ACETYLCHOLINE IN ANEMIC HYPDXIA Masahisa Shimada 1 , Tomio Imahayashi 1 , Hiroki S. Ozaki 1 1Department of Anatomy, Kagawa Medical School pp.1189-1194
Published Date 1985/12/1
DOI https://doi.org/10.11477/mf.1406205628
  • Abstract
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Pretreatment of mice with 4-(o-benzylphenoxy)- N-methylbutylamine hydrochloride (bifemelane) protected against effects of anemic hypoxia. Befe-melane delayed the loss of the righting reflex (from 17.8±1.3 to 21.9±1.2 min, p<0.05) and death (from 19.6±1.3 to 23.3±1.1, p<0.05) in micewith anemic hypoxia (induced with NaNO2). Pretreatment with bifemelane ameliorated the reduction in the synthesis of acetylcholine from labeled precursors in anemic hypoxia. Namely, it reduced the inhibition of acetylcholine synthesis from labeled choline (from 3.8±0.5 to 9.4±1.2 pmole/mg protein at 30 mg/kg, p<0.01), but not significant at 15 mg/kg. However it (15 mg/kg) caused a significant increase in the incorporation of (U-14C) glucose into acetylcholine compared to the value for hypoxic animals (from 5±0.5 to 9±1 dpm/mg protein, p<0.001). Under normal conditions, concentrations of acetylcholine and glucose in the brain were significantly increased by the 30 mg/kg of bifemelane, while the synthesis of acetylcholine from choline was significantly decreased. This reduction of synthesis might be caused by the increased acetylcholine concentra-tions in the brain. Fifteen mg/kg of bifemelane significantly increased the concentrations of glu-cose, 14C-acid soluble fraction and the synthesis of acetylcholine from (U-14C) glucose. In the in vitro experiments, cholinesterase activity was significantly inhibited by the bifemelane (1.47 μM). However, its inhibitory effects were about 1/9000 of physostigmine sulfate, which might be too weak to increase the acetylcholine concentration in the brain. Therefore, causative factors responsible for the elevation of acetylcholine by the befemelane is still unclear. However, it might be certain that the reductions in the synthesis of acetylcholine induced with the anemic hypoxia were ameliorated from the two different roots, i. e. choline and acetyl moieties. Among the rest, the protection of bifemelane against the hypoxia might be more effective in the acetyl moiety.


Copyright © 1985, Igaku-Shoin Ltd. All rights reserved.

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電子版ISSN 2185-405X 印刷版ISSN 0006-8969 医学書院

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