PRECLINICAL FINDINGS OF NEW CYCLOHEXILAMMONIUM SALT 2-[1-ETHYL-3-METHYL-7-(DIOXOTHIETANYL-3)XANTHINYL- 8-THIO]ACETIC ACID WITH RESPECT TO HEMOSTASIS SYSTEM UNDER CONDITIONS IN VITRO

Issue: 
8
Year: 
2016

A.V. Samorodov
Ph.D. (Chem.), Assistant, Department of Biochemistry, Bashir State Medical University (Ufa)
E-mail: avsamorodov@gmail.com
F.Kh. Kamilov
Dr.Sc. (Med.), Professor, Head of Department of Biochemistry, Bashir State Medical University (Ufa)
F.A. Khaliullin
Dr.Sc. (Pharm.), Professor, Head of Department of Pharmaceutical Chemistry with courses of Analytical and Toxicological Chemistry,
Bashir State Medical University (Ufa)
Y.V. Shabalina
Ph.D. (Pharm.), Associate Professor, Department of Pharmaceutical Chemistry with courses of Analytical and Toxicological Chemistry,
Bashir State Medical University (Ufa)
A.R. Khalimov
Post-graduate Student, Department of Biochemistry, Bashir State Medical University (Ufa)
D.Z. Murataev
Post-graduate Student, Department of Pharmaceutical Chemistry with courses of Analytical and Toxicological Chemistry,
Bashir State Medical University (Ufa)
A.I. Samorodova
Ph.D. (Med.), Assistant, Department of Biochemistry, Bashir State Medical University (Ufa)

The paper shows preclinical findings of new cyclohexilammonium salt 2-[1-ethyl-3-methyl-7-(dioxothietanyl-3)xanthinyl-8-thio]acetic acid under intraperitoneal injection in rats and its comparison with analog product of pentoxifylline. The impact of firstly synthesized derivative xantine and pentoxifylline on the functional activity of platelets under conditions in vivo was studied with the help of a laser analyzer of platelet aggregation Biola 230 LA (Russia). Adenosinediphosphate, collagen, epinephrine and ristocetin were used as an aggregation inducer. Aggregatograms were analyzed with the help of AGGR software. Thromboelastography (TEG 5000, Haemoscope Corporation, USA) was performed in accordance with instructions of the manufacture and performed within 1 h of blood sampling. Thromboelastography parameters of reaction time, angle and maximal amplitude and conventional coagulation data of platelet count. Activity of factor 3 platelets was defined in accordance with the V. Rabiner method. Definition of factor 4 platelets was carried out under the effect that heated plasma poor in platelets exerts on thrombin-heparin time of plasma coagulation according to the L.A. Matviyenko and M.A. Kotovschikaya method. Release of P3 и P4 factors during platelet aggregation was appraised after aggregation carried out by adenosinediphosphate and centrifugation. The research has determined that new cyclohexilammonium salt is exceeds pentoxifylline spectrumwise and levelwise in terms of antiaggregational activity. The findings show the absence of the second wave of platelet aggregation induced by small doses of ADP, prolongation of lag-period under collagen-induced platelet aggregation as well as the reduced availability and release of platelet factors 3 and 4 which proves the affect of new cyclohexilammonium salt 2-[1-ethyl-3-methyl-7-(dioxothietanyl- 3)xanthinyl-8-thio]acetic acid as a potential inhibitor of platelet release reaction.

Keywords: 
Key words: 1-ethylxanthine derivatives
hemostasis
antiaggregation activity
platelet release reaction.