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Autoradiographic distribution of 14C-hemicholinium-3 in mouse whole body and dog brain.

14 C-Hemicholinium-3 iodide ( 14 C-HC-3) labeled in the methyl groups of the quaternary nitrogens (1.9 mc/100 mg) was administered intravenously to mice in a dose of 5 mg/kg and intraventricularly to dogs in doses of 0.5 to 1.0 mg under N 2 O-O 2 anesthesia to study its autoradiographic distribution. Mice were sacrificed at 30 seconds and 10 minutes after injection. At 30 seconds, radioactivity was present throughout the body and especially in the heart cavities, lungs, kidneys, adrenals, liver, salivary glands and heart muscle in decreasing order. At 10 minutes, most of the radioactivity was markedly reduced except for the kidneys which appear to be the major organ of excretion. Very little radioactivity was observed in the central nervous system, suggesting a blood-brain barrier to this substance. In dogs 0.5 and 1.0 mg of 14 C-HC-3 (15.3 and 30.6 µc) given intraventricularly showed predominant distribution on the side of injection. It was present 5 minutes to 4 hours after injection along the walls of the ventricles and later tended to accumulate especially in the caudate nucleus and hippocampus. A quantitative study measuring the actual distribution of radioactivity and acetylcholine in the dog brain indicated that the reduction of acetylcholine was partially related to the concentration of 14 C-HC-3 as follows: caudate > hippocampus > medial thalamus = amygdala > reticular formation. Because radioactivity extracted from brain homogenates containing 14 C-HC-3 had the same R f values as control 14 C-HC-3, it was concluded that the radioactivity in various brain areas was due to 14 C-HC-3 itself or a metabolite with identical migrating characteristics.