Interactions of antiarrhythmics with artificial phospholipid membranes.
Binding of antiarrhythmics to phospholipids has been quantified by measuring the drug-induced fluorescence increase in 8-anilino-1-napthalenesulfonate (ANS)-treated phosphatidylcholine membranes. The ability of test compounds to increase fluorescence intensity to 50% varies between 1.3 and 88 X 10(-6) M, exhibiting a potency ratio of 1.8 log units. The antiarrythmics tested in this study exhibited a wide spectrum of lipophilicity ranging between sigma f = 6.66 for the most lipophilic compound asocainol, to sigma f = 1.21 for the most hydrophilic compound procainamide. The pKa values ranged from 10.80 for quinacainol to 6.26 for ethmozine. Consequently, the test compounds are 99.9 to 6.8% protonated at physiological pH. Binding of antiarrythmics to phosphatidylcholine membranes appears to be determined mainly by their lipophilicity (r = 0.91), irrespective of the pKa, as demonstrated for ethmozine and lidocaine which showed an excellent fit to the regression line. Binding of a variety of antiarrhythmics (n = 8) to phosphatidylcholine appeared to correlate significantly with the mean daily dosage for these drugs (r = 0.97).
Voigt
W
W
Department of Clinical Physiology, University of Düsseldorf, Federal Republic of Germany.
Mannhold
R
R
Limberg
J
J
Blaschke
G
G
D000889:Anti-Arrhythmia Agents / Q000032:analysis*; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D008567:Membranes, Artificial; D010743:Phospholipids / Q000032:analysis*; D013050:Spectrometry, Fluorescence
D000889:Anti-Arrhythmia Agents; D008567:Membranes, Artificial; D010743:Phospholipids