Giarman_1964_Br.J.Pharmacol.Chemother_23_123

A number of centrally acting cholinolytic drugs reduced levels of cerebral acetylcholine in the rat. Among its naturally occurring analogues, hyoscine had the greatest potency, producing a decrease of 31% at a dose of 0.63 mg/kg. Atropine methyl nitrate, which acts as a cholinolytic drug in the periphery, had no effect on brain acetylcholine levels. The fall in acetylcholine produced by hyoscine was greatest after 60 min and disappeared at about 120 min. The animals tended to show a partial tolerance to this effect of hyoscine when the drug was administered repeatedly. The reduction in acetylcholine after hyoscine was restricted to the cerebral hemispheres, and did not appear in subcortical regions of the brain. Hyoscine had no influence on the net synthesis of acetylcholine by acetone-extracted powder of rat brain. In a series of four synthetic cholinolytic drugs, only the two with conspicuous psychotomimetic actions in man produced a decrease in brain acetylcholine comparable to that seen with hyoscine and related alkaloids.