N. Dzimiri et Aa. Almotrefi, ACTIONS OF AMIODARONE ON MITOCHONDRIAL ATPASE AND LACTATE-DEHYDROGENASE ACTIVITIES IN GUINEA-PIG HEART PREPARATIONS, European journal of pharmacology, 242(2), 1993, pp. 113-118
The effects of amiodarone on mitochondrial ATPase (EC 3.6.1.3) and lac
tate dehydrogenase (LDH: EC 1.1.1.27) activities were studied in guine
a pig mitochondrial preparations in order to test the hypothesis that
amiodarone exerts some of its effects as a result of multiple actions
on membrane-bound enzymes and receptors. Amiodarone inhibited the ATPa
se activity in the range of 10 pM to 10 mM (n = 10) with IC50 values o
f 56.4 +/- 7.2 muM. However, although the inhibitory action was very s
ignificant (P < 0.0001, compared to the control) in the concentration
range of 100 pM to 10 muM, the differences in individual enzyme respon
ses showed very weak correlation with drug concentration. In this regi
on, the inhibitory effects were almost constant at approximately 37%.
Below 100 pM and above this range however, the concentration-response
relationships were steep, reaching total inhibition at approximately 2
.5 mM. Amiodarone also exerted concentration-dependent inhibitory effe
cts on lactate dehydrogenase activity. However, over the effective inh
ibitory concentration range (5-95%) of 7.5 muM to 2.5 mM (n = 8) and I
C50 value of 108 +/- 6 muM, its inhibitory potency was twofold weaker
than that of its ATPase inhibition. We propose that these actions cont
ribute, at least in part, to the mechanism(s) of some of the pharmacol
ogical actions of amiodarone.