EARLY RESPIRATORY DEPRESSION BY CURARE AND CURARE-POTASSIUM ANTAGONISM

¹ Department of Pharmacology, Harvard Medical School, Boston, Massachusetts
² Laboratory of Pharmacology, University of Pennsylvania, Philadelphia, Pennsylvania

It has been shown that early thoracic respiratory depression can occur in mammals with chloralose anesthesia but not with other anesthetics, following a comparatively small dose of curare which is too weak to diminish the single twitch tension of a non-respiratory skeletal muscle, although the Wedensky inhibition is shown to he profoundly intensified and the post-tetanic facilitation to he more permanently and strikingly abolished. Intocostrin and d-tubocurarine show the same depressant effects but dihydro--erythroidine displayed some minor difference in dogs. The underlying mechanism is not central, but a peripheral effect on the intercostal muscles, and the apparently unaffected single twitches are in interesting contrast to intensified Wedensky inhihition and abolition of post-tetanic facilitation. This respiratory depression is easily antagonized by eserine and K⁺. The widespread impression that the respiratory muscles are relatively resistant to curare therefore is unjustified as far as the intercostal muscles of dogs, cats and rabbits are concerned, though it probably is still valid for the diaphragm.

It is a great pleasure to record our indebtedness to Miss Nancy M. Bulkley and Mr. T. Bruce Vest who assisted in some of our experiments and to Mr. L. H. Ashe and Messrs. E. H. Squibb and Sons who supplied us with Intocostrin and d-tuhocurarine chloride.