THE EFFECT OF CO2-INDUCED ACID-BASE CHANGES ON THE POTENCIES OF MUSCLE-RELAXANTS AND ANTAGONISM OF NEUROMUSCULAR BLOCK BY NEOSTIGMINE IN RAT IN-VITRO

We investigated the influence of CO2-induced acid-base changes on the potencies of the monoquaternary relaxants (rocuronium, vecuronium, and d-tubocurarine) and bisquaternary relaxants (pancuronium, pipecuroniu m, and metocurine), and on the antagonism of their neuromuscular block by neostigmine. Phrenic nerve-hemidiaphragm preparations of rats were used. The pH changes were induced by changing the CO2 concentration a erating the modified Krebs solution. The potencies of the monoquaterna ry relaxants increased at 9% CO2 (pH 7.2) and decreased at 2.5% CO2 (p H 7.6) from those of 5% CO2 (pH 7.4) both with and without neostigmine (P < 0.05), whereas the potencies of the bisquaternary drugs did not change significantly at different pH levels from control (pH 7.4) both with and without neostigmine. The slopes of the log concentration-per cent response curves of each drug were not significantly different at each pH level. The ratios of inhibitory concentration, 50% (IC50) valu es with and without neostigmine at each pH value for each drug were no t significantly different indicating that the neostigmine-induced anta gonism for each drug was not affected by the CO2-induced acid-base cha nges. But the ratios of the IC50 values of the relaxants (rocuronium, vecuronium, pancuronium, and pipecuronium) were significantly lower (P < 0.05) than those of the isoquinolinium drugs (d-tubocurarine and me tocurine) at each pH level, suggesting that the antagonism is enhanced at each pH level for the isoquinolinium relaxants. The difference was independent of their monoquaternary or bisquaternary nature. These re sults suggest that CO, increases the potency of the monoquaternary rel axants but does not affect the bisquaternary relaxants. The different effects shown by the steroidal and isoquinolinium relaxants due to aci d-base changes on neostigmine-induced antagonism may be attributed to their structural difference and different mode of action of the muscle relaxants.