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• W2059796887 abstract "The effects of Class I antiarrhythmic drugs on the maximum rate of depolarization (Vmax) of guinea-pig ventricular action potentials were studied by standard microelectrode techniques. The ability of seven different drugs to depress Vmax in unstimulated tissue ('resting block') was found to correlate poorly with the lipophilicity (log P) of the compounds and only a little better with their molecular weights. Depression of Vmax in stimulated tissue was studied for 11 drugs and found, in all cases, to increase with stimulation frequency ('rate-dependent block'). The rapidity of onset of rate-dependent block (at approximately equipotent concentrations) varied markedly between drugs. It correlated well with molecular weight (r = 0.83; P less than 0.01). The time constant of recovery from rate-dependent block (tau re) also correlated very well with molecular weight (r = 0.94; P less than 0.001) for the seven drugs thus studied. A simplified model for the interaction of Class I drugs with the fast sodium channel is proposed in which the drugs all act as 'inactivation enhancers' (as suggested by other workers) but in which their molecular weight plays a central role in determining the kinetics of this interaction." @default.
• W2059796887 created "2016-06-24" @default.
• W2059796887 creator A5073337654 @default.
• W2059796887 date "1983-09-01" @default.
• W2059796887 modified "2023-10-17" @default.
• W2059796887 title "Importance of physico-chemical properties in determining the kinetics of the effects of Class I antiarrhythmic drugs on maximum rate of depolarization in guinea-pig ventricle" @default.
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• W2059796887 doi "https://doi.org/10.1111/j.1476-5381.1983.tb11046.x" @default.
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