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Journal of Pharmacology And Experimental Therapeutics, Vol. 103, Issue 1, 35-43, 1951
Copyright © 1951 by American Society for Pharmacology and Experimental Therapeutics

EFFECTS OF CONVULSANT AND NARCOTIC DRUGS ON ACETYLCHOLINE SYNTHESIS

Hugh McLennan 1 and K. A. C. Elliott 1

1 Department of Neurology and Neurosurgery, McGill University, and the Montreal Neurokgical Institute, Montreal, Canada

The synthesis of free acetylcholine (ACh) by brain slices under optimal conditions (oxygen, glucose, bicarbonate buffer, 27 mM potassium, 1.3 mM calcium in isotonic solution) is accelerated by very low concentrations and inhibited by higher concentrations of a variety of convulsant and narcotic or anticonvulsant drugs.

When two drugs are present together, each in a concentration which alone causes acceleration, inhibition occurs. The extent of this inhibition is greater than would be obtained with a considerably higher concentration of either drug alone.

The drugs will not replace potassium as a stimulant of synthesis. No obvious effect on bound ACh was observed.

Similar effects of single and pairs of drugs on ACh synthesis by cell-free brain extracts were obtained though the inhibitory effects of high concentrations were much less marked.

The concentrations of narcotics which produce inhibition with slices in vitro correspond to the estimated concentration in vivo during narcosis. The concentrations of water soluble convulsant drugs which cause acceleration in vitro correspond to the estimated concentration when convulsions are produced in vivo.

Methionine sulfoximine, the toxic factor of nitrogen trichloride-treated flour, exerts stimulatory and inhibitory effects on ACh synthesis like the other drugs. The substance from 1-methionine is more active than that from dl-methionine.

Submitted on May 25, 1951




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Copyright © 1951 by the American Society for Pharmacology and Experimental Therapeutics.