A comparison of effects measured with isotonic and isometric recording: II. Concentration‐effect curves for physiological antagonists

If one drug, B, antagonizes another, A, by producing the opposite physiological effect, the antagonist concentration‐effect curves should be affected by the recording system, which limits the range of agonist responses. With pieces of isolated guinea‐pig ileum taken from adjacent parts of the same animal, one recorded isotonically, the other isometrically with the same load, the isotonic IC 50 values for (−)isoprenaline opposing carbachol or histamine were lower than the isometric values ( P <0.01) but there was a significant correlation between them ( P <0.01): the isotonic curves were steeper ( P <0.01) and there were wider shifts in IC 50 before increasing the agonist reduced the maximum relaxation. In similar experiments with pieces of rat uterus in oestrus from the same animal, the concentration‐effect curves for carbachol opposed by increasing concentrations of (−)isoprenaline or (−)adrenaline had slightly lower EC 50 values with isometric recording but there was a significant correlation ( P <0.01) with isotonic values. The antagonist effect (ratio of the EC 50 relative to that for the control) was higher with isotonic recording ( P <0.01 for (−)isoprenaline, P <0.025 for (−)adrenaline) and all (27) curves were steeper than the corresponding isometric curve ( P <0.001). The influence of the method of recording on the results is expected from the narrower operational window and smaller upper limit to relaxation with isotonic recording. A way of obtaining measurements of IC 50 against a standard agonist effect is suggested in an Appendix.British Journal of Pharmacology (2001) 133 , 1087–1095; doi: 10.1038/sj.bjp.0704169