The effect of buthobendin (CravitenR) on the ATPase activities/total (Na, K, Mg)-ATPase, and the ouabaine-sensitive (Na, K-ATPase) and insensitive (Mg-ATPase) fractions/from human erythrocyte membrane was examined in the presence or absence of liposomes. The activities of both ATPase fractions increased by 250% in the presence of 10 mmol/l phosphatidylcholine. Buthobendin inhibited both ATPases, but especially Na, K-ATPase. This inhibitory effect was much greater in the hydrophobic milieu of liposomes. The inhibitory effect was proportional to the drug concentration and was stereospecifically related only to the 2S, 2'S isomer. Isomer 2R, 2'R and epinephrine used for comparison did not show any similar inhibitory influence. The decrease in ouabaine-sensitive ATPase activity under the influence of buthobendin might cause changes in cation distribution and cell membrane polarization. An inhibitory effect was also observed in vivo, after single iv administration of buthobendin to patients with ventricular arrhythmias and elevated activities of both erythrocyte membrane ATPases. Complete normalization of cardiac rhythm in about 30% of patients was accompanied - in the sensitive group of patients - with a decrease in Mg-ATPase activity without any changes in elevated Na, K-ATPase activity. In the group of patients resistant to buthobendin therapy both ATPases remained unchanged.
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