Aprindine inhibits calmodulin-stimulated phosphodiesterase and Ca-ATPase activities.

Article Details

Citation

Levine SN, Hollier B

Aprindine inhibits calmodulin-stimulated phosphodiesterase and Ca-ATPase activities.

J Cardiovasc Pharmacol. 1983 Jan-Feb;5(1):151-6.

PubMed ID
6186851 [ View in PubMed
]
Abstract

Aprindine, an antiarrhythmic agent with structural similarities to lidocaine and procainamide, has proved effective in treatment of patients with ventricular premature depolarizations, ventricular tachycardia, and supraventricular arrhythmias. While its effects at an electrophysiologic level have been elucidated, its mechanism of action at a biochemical level has remained largely undefined. The data in this communication demonstrate that aprindine inhibits the activation of bovine brain cyclic 3':5'-nucleotide phosphodiesterase (EC 3.1.4.17) by calmodulin. This inhibition is specific for the calmodulin-stimulated enzyme, as no effect of aprindine is seen when phosphodiesterase is assayed in the absence of calmodulin. The inhibition is competitive with respect to substrate (cyclic AMP) and calmodulin concentrations. In the presence of 10 nM calmodulin, the ID50 for aprindine is 18 microM. This inhibition is not the result of aprindine acting as a calcium chelator because increasing the calcium concentration does not reverse the inhibitory effect. Aprindine also inhibits calmodulin-stimulated Ca-ATPase (ATP phosphohydrolase EC 3.6.1.3) activity, but again has no effect on the enzyme in the absence of calmodulin. Aprindine has hydrophobic properties which may be responsible for the inhibitory effect. Sufficient concentrations of aprindine are achieved in myocardial tissues to interfere with the ability of calmodulin to stimulate a number of enzymes present in the heart.

DrugBank Data that Cites this Article

Drug Targets
DrugTargetKindOrganismPharmacological ActionActions
AprindineCalmodulinProteinHumans
Unknown
Inhibitor
Details