Pretreatment of mice with 4-(o-benzylphenoxy)-N-methylbutylamine hydrochloride (
bifemelane) protected against effects of anemic
hypoxia. Befemelane delayed the loss of the righting reflex (from 17.8 +/- 1.3 to 21.9 +/- 1.2 min, p less than 0.05) and death (from 19.6 +/- 1.3 to 23.3 +/- 1.1, p less than 0.05) in mice with 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 less than 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 less than 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 concentrations in the brain. Fifteen mg/kg of
bifemelane significantly increased the concentrations of
glucose, 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 microM). However, its inhibitory effects were about 1/9000 of
physostigmine sulfate, which might be too weak to increase the
acetylcholine concentration in the brain.(ABSTRACT TRUNCATED AT 250 WORDS)