Temperature and potency of d-tubocurarine and pancuronium in vitro

The concentrations of d-tubocurarine and pancuronium producing 50% block of the indirectly elicited twitch were determined in isolated mouse nerve-diaphragm preparations at 37 and 25 C. The contralateral side was used as a control in a 2 x 2 factorial analysis of variance. Cooling shifted the dose-response curves for both drugs to the left, but only slightly (from 1.69 +/- 0.022 microM to 1.49 +/- 0.021 microM with d-tubocurarine and from 0.65 +/- 0.012 microM to 0.46 +/- 0.009 microM with pancuronium). The dose-response relationship was, however, so steep (Hill coefficient approximately 5 to 6) that a slight horizontal shift of the dose-response curve corresponds to a considerable decrease in the twitch response at a concentration midway between the curves. Thus, studies using only the concentration that produces partial block of twitch responses misleadingly suggest a large effect of temperature. Similarly, if in another system the curve were to shift to the right even only slightly, a temperature effect in the reverse direction might be reported. It is concluded that temperature appears to have little influence on cellular potency of neuromuscular blocking agents.