Chiou C Y, Malagodi M H, Sastry B V, Posner P
J Pharmacol Exp Ther. 1976 Aug;198(2):444-9.
6-(N, N-Diethylamino) hexyl-3, 4, 5-trimethylbenzoate (TMB-6) and lidocaine were equipotent (1 mg/kg) in the conversion of ectopic rhythms to normal rhythms in digoxin-toxic dogs. However, TMB-6 had fewer side effects on heart rates and dp/dt than lidocaine. TMB-6 inhibited the contractile force of electrically stimulated dog and guinea-pig atria and ventricles at concentrations ranging from 2.5 X 10(-5) to 1.7 X 10(-4) M. Elevation of extracellular Ca++ concentrations from 2.7 to 5.4 mM produced a significant increase in the ID50 of TMB-6 in atria (from 2.5 X 10(-5) to 5.0 X 10(-5) M in dogs and from 7.2 X 10(-5) to 1.0 X 10(-4) M in guinea pigs). TMB-6 (7.3 X 10(-5) to 2.4 X 10(-4) M) depressed the amplitude of Ca++-dependent action potentials in depolarized dog cardiac Purkinje fibers. These results are discussed with regard to the antagonism of TMB-6 on Ca++ availability in the myocardium which leads to the conversion of cardiac arrhythmias.
6-(N,N-二乙氨基)己基-3,4,5-三甲基苯甲酸酯(TMB-6)和利多卡因在将地高辛中毒犬的异位心律转为正常心律方面效力相当(1毫克/千克)。然而,TMB-6对心率和dp/dt的副作用比利多卡因少。TMB-6在浓度范围为2.5×10^(-5)至1.7×10^(-4)M时,能抑制电刺激的犬和豚鼠心房及心室的收缩力。将细胞外Ca++浓度从2.7毫摩尔/升提高到5.4毫摩尔/升,会使TMB-6在心房中的半数抑制浓度(ID50)显著增加(犬从2.5×10^(-5)升至5.0×10^(-5)M,豚鼠从7.2×10^(-5)升至1.0×10^(-4)M)。TMB-6(7.3×10^(-5)至2.4×10^(-4)M)可降低去极化犬心脏浦肯野纤维中Ca++依赖性动作电位的幅度。就TMB-6对心肌中Ca++可用性的拮抗作用导致心律失常的转变这一点对这些结果进行了讨论。