PubMed · 431563
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J Koch-Weser. 1979-04-26. Disopyramide.. https://doi.org/10.1056/nejm197904263001705
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Based on the gate-related receptor hypothesis, a quantitative study on kinetics and state-dependency of metoclopramide (Met) blockade of cardiac sodium channels was performed by computer simulation. The characteristics of Met, a sodium channel blocker modulated simultaneously by both activation and inactivation gates were described and analyzed for the first time. The time constant of recovery from blocking for Met at resting potential -85 mV was 2.82 s, which was increased during depolarization or hyperpolarization. Its apparent rate of onset of blocking was 0.49 AP-1 at a stimulation frequency of 2.0 Hz. A concentration-dependent shift of h infinity curve was found at doses higher than 100 mumol/L Met. This study provides a new test and verification for our gate-related receptor hypothesis.