Research Results in Pharmacology 3(2): 3-13, doi: 10.18413/2313-8971-2017-3-2-3-13
PLEYOTROPIC ANTIAGGREGANT EFFECTS OF AN INNOVATIVE ANTIARRHYTHMIC OF CLASS III SS-68, AN INDOLE DERIVATIVE
expand article infoSaida K. Bogus, Aleksandr S. Dukhanin, Aida F. Kucheryavenko, Dmitry V. Vinakov, Konstantin Suzdalev, Pavel Alexandrovich Galenko-Yaroshevsky
Open Access
Abstract
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).
Keywords
SS-68 compound, platelet aggregation, disaggregation, intracellular calcium, molecular targets of anti-platelet effect.