STUDIES ON THE INTER-RELATIONSHIP OF CERTAIN CHOLINERGIC COMPOUNDS

IV. Anti-Curare Action in Anesthetized Man

¹ Departments of Surgery (Anesthesia) and Pharmacology, Cornell University Medical College and The New York Hospital, New York 21, N. Y.

1. A method is described which provides a simple means for the quantitative evaluation of a curariform action in the anesthetized surgical patient.

2. The anti-curare actions of 3-hydroxy phenyltrimethylammonium bromide (Nu 2561), 3-acetoxy phenyltrimethylammonium methylsulfate (Nu 2107) and 3-hydroxy phenyldimethylethylammonium bromide (Ro 2-3198) were evaluated in anesthetized man. Each of these agents proved to be an effective antagonist to d-tubocurarine chloride. The dose-response curves are such that 5 mgm. of agent are required to antagonize a level of curarization which is about 50 per cent complete; doses of 10 and 15 mgm. are required when the degree of curarization is approximately 70 and 90 per cent of a complete effect, respectively.

3. Multiple doses are effective and within the dose range mentioned there is no evidence of cumulation of the anti-curare agents or of synergism with d-tubocurarine.

4. In the presence of ether moderately larger amounts of agent are required to antagonize curare than is the case in the presence of cyclopropane.

5. Although the evidence indicates that the duration of action of these quaternary ammonium compounds is very brief, their resultant effect is sustained. If an adequate dose is given on the first administration no repeated injections are necessary.

6. The only prominent side action of Nu 2561, Nu 2017 or Ro 2-3198 is the production of a transient cardiac slowing. This slowing is more pronounced with larger doses and occurs most frequently and to a greater degree with cyclopropane than with ether. Bronchoconstriction and excessive secretion have been observed in asthmatic patients. The administration of atropine prevents or abolishes all undesirable side actions.

This article has been cited by other articles:

				H. H. Su, F. T. Kao, and M. Karp The Respiratory Effect of Ro 2-3198 (3-Hydroxy Phenyldimethylethylammonium Bromide) in Syncurinized Dogs Science, June 29, 1951; 113(2948): 743 - 745. [PDF]