Sodium channel blockers: the size/solubility hypothesis revisited.
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.
Courtney
K R
KR
Palo Alto Medical Foundation, California 94301.
D000319:Adrenergic beta-Antagonists / Q000493:pharmacokinetics*; D000818:Animals; D001693:Biological Transport, Active; D015195:Drug Design; D006168:Guinea Pigs; D008564:Membrane Potentials; D008958:Models, Molecular; D008970:Molecular Weight; D015222:Sodium Channels / Q000187:drug effects / Q000378:metabolism*; D012995:Solubility
D000319:Adrenergic beta-Antagonists; D015222:Sodium Channels