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KR Courtney
Palo Alto Medical Foundation, California 94301.
The influence that drug size has on the rate of recovery of sodium channels in heart tissue has been reexamined. A drug dimension that looks at the end-on view of the molecule provides a substantially better explanation for the size dependence of repriming kinetics than does molecular weight. A quantitative model for the recovery time is provided that couples proton exchange kinetics with a drug size- dependent process that is related to recovery from inactivation. Drugs having a wider span at their aromatic end produce more slowing of the rate of recovery from inactivation.
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