Pleyotropic antiaggregant effects of an innovative antiarrhythmic of class III SS-68, an indole derivative

Аннотация

Background: A new indole derivative with the lab code-number SS-68 demonstrates a   significant antiarrhythmic (anti-fibrillation) activity associated with the predominant influence on   potassium and calcium conductivity of cardiomyocytes plasmalemmas. The preliminary data give   evidence of SS-68 possessing an antiaggregant activity.

Methods: The influence of SS-68 on the platelet formation stage of hemostasis was determined   by assessment of the anti-platelet effect (measuring platelet aggregation with Born/ O’Brien   method), the dynamics of intracellular concentration of calcium ions in platelets was studied with   FURA-2/АМ fluorescent probe.

Results: Relative efficiency of the SS-68 indole derivative influence on platelet aggregation with   the use of various inducers decreases in the following order: collagen > serotonin > ADP. The   influence of SS-68 on platelet activity is characterized by pleiotropic effects: calcium-blocking   effect, potentiation of cAMP-response, suppression of intracellular mechanisms of transmitting a   stimulating signal, caused by the activation of collagen receptors.

Conclusion: G-proteins are the most likely molecular targets of pleiotropic antiaggregant effect   of SS-68. A more than threefold increase in the anti-platelet effect of SS-68 in vivo suggests the   development of an active metabolite (metabolites).