STUDIES ON THE INTER-RELATIONSHIP OF CERTAIN CHOLINERGIC COMPOUNDS

V. The Significance of the Actions of the 3-Hydroxy Phenyltrimethylammonium Ion on Neuromuscular Function

¹ Department of Pharmacology, Cornell University Medical College, New York 21, N.Y.

The pharmacologic effects of 3-hydroxy phenyltrimethylammonium bromide (Nu 2561) are characterized by a high specificity for the neuromuscular junction. Accordingly, the effects of this substance on neuromuscular function were demonstrated in the cat. These actions include:

(1) the production of a characteristic acetylcholine-like response in chronically denervated muscle,

(2) the augmentation of the contractile response of innervated muscle to single maximal motor nerve stimuli,

(3) the production of repetitive and asynchronous propagated potentials in response to a single maximal motor nerve shock,

(4) a prominent anti-curare action,

(5) a transient curariform effect that is antagonized reciprocally by curare and

(6) potentiating effects on neuromuscular function that cannot be enhanced significantly by cholinesterase inactivation.

The duration of action of Nu 2561 at the junctional region is brief (approximately three minutes) but despite this, its anti-curare effect is permanent.

These findings are discussed with relation to their implications concerning the actions of related substances on neuromuscular function. In addition, an hypothesis is presented to explain the way in which Nu 2561, and probably related agents, effect de-curarization.

Finally, the data are discussed with regard to the significance of the 3-hydroxy phenyltrimethylammonium structure for musculotropic activity.

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				W. F. Riker Jr. Pharmacologic Considerations in a Reevaluation of the Neuromuscular Synapse Arch Neurol, November 1, 1960; 3(5): 488 - 499. [Abstract] [PDF]