CORRELATION BETWEEN PHARMACOLOGICAL RESPONSES TO BENZOYLCHOLINE, METHACHOLINE AND ACETYLCHOLINE AND ACTIVITY OF CHOLINESTERASES

¹ Department of Pharmacology and Materia Medica, Georgetown University School of Medicine, Washington 7, D. C.

The pharmacological responses to cholinergic agents were studied prior to and after administration of anticholinesterase drugs and correlated with the activities of pseudo- and acetyl-cholinesterase determined manometrically in blood, muscle and neuro-effectors.

In non-atropinized animals benzoylcholine caused limited vasodepression (up to 30 mm. Hg) and stimulation of gastrointestinal motility in doses of 0.01 to 0.2 mgm. per kgm. These effects did not increase over the range indicated and were easily inhibited or converted into pressor and intestinal inhibitory responses by small doses of atropine.

Larger doses of benzoylcholine caused transient respiratory stimulation, intestinal inhibitory and vasopressor effects even in non-atropinized animals. The dose-effect relationship was similar to that obtained for acetylcholine in atropinized animals.

The pressor and intestinal inhibitory effects of benzoylcholine are due to sympathetic ganglionic stimulation and they are abolished by ganglionic blocking agents but not by adrenalectomy. The respiratory stimulation produced by nicotinic doses of benzoylcholine may he abolished by section of the vagi above the ganglia nodosa and removal of the carotid bodies.

DFP and other cholinesterase inhibitors convert muscarinic effects to small doses of benzoylcholine into nicotinic effects and potentiate nicotinic effects of the larger doses.

The degree of benzoylcholine potentiation by DFP follows closely inhibition of pesudocholinesterase activity in the blood. The maximum potentiation effect is obtained with doses of DFP which completely inhibit pseudocholinesterase but do not affect acetylcholinesterase (0.05 to 0.10 mgm. per kgm.).

Pharmacological responses to acetylcholine are first potentiated by doses of DFP which not only inhibit pseudocholinesterase but significantly inhibit acetylcholinesterase of blood and of effectors (0.5 mgm.).

Pharmacological responses to methacholine are not potentiated by DFP (up to 8 mgm.) or by other anticholinesterasic drugs (hexaethyl tetraphosphate and physostigmine).

The significance of these findings is discussed. The importance of cholinesterases of circulating body fluids ("transport" cholinesterases) in controlling the fate of certain cholinergie agents prior to their reaching the neuro-effectors is stressed.

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