sodium-nitrite and bifemelane

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)

Topics: Acetylcholine; Animals; Benzhydryl Compounds; Brain; Cholinesterases; Enzyme Activation; Hypoxia, Brain; In Vitro Techniques; Male; Mice; Mice, Inbred ICR; Sodium Nitrite