2020 / 01

Next Paper
DOI: 10.24075/brsmu.2020.010

ORIGINAL RESEARCH

Study of the new 4-phenylpyrrolidinone-2 derivative pharmacokinetics and neuroprotective effect in the ischemic stroke animal model

Borozdenko DA, Lyakhmun DN, Golubev YaV, Tarasenko DV, Kiseleva NM, Negrebetsky VV
About authors

Pirogov Russian National Research Medical University, Moscow, Russia

Correspondence should be addressed: Denis A. Borozdenko
Ostrovityanova, 1, Moscow, 117997; ude.hcetsyhp@oknedzorob

About paper

Funding: the study was performed as a part of the 2018–2020 Pirogov Russian National Research Medical University public assignment, R&D registration № АААА-А18-118051590108-1.

Acknowledgements: to Kamkin AG PhD, head of the department of Physiology of the Faculty of Biomedicine, head of the laboratory of Electrophysiology of the Institute of Translational Medicine of Pirogov Russian National Research Medical University for the opportunity to use the equipment of the Scientific and Educational Center for the study of molecular and cellular mechanisms of hypoxia and ischemia; to Abakumov MA PhD, associate professor of the department of Medical Nanobiotechnology of the Faculty of Biomedicine, for his assistance in modelling, MRI scanning and interpretation of the results.

Author contribution: Borozdenko DA — working with animals, primary data acquisition and analysis, manuscript writing; Lyakhmun DN — working with animals, functional testing; Golubev YaV — substance concentration analysis; Tarasenko DV — synthesis of substance; Kiseleva NM — study design, study management, manuscript preparation; Negrebetsky VadV — study design, study management.

Received: 2020-01-28 Accepted: 2020-02-11 Published online: 2020-02-23
|
Fig. 1. VRF_11 kinetics in blood plasma after the single intravenous administration at a dose of 250 mg/kg
Fig. 2. * — p < 0.05 (comparison of mean values in relation to the control group); ** — p < 0.07 (there is a tendency to significant differences when comparing average values in relation to the control group). Animal behavior during the hole board test on the 10th day after ischemia modeling
Table 1. VRF_11 pharmacokinetics study design (single intravenous administration)
Table 2. VRF_11 blood level in laboratory animals after single intravenous administration at a dose of 250 mg/kg (n = 6, µg/ml)
Note: М — mean value for the time point; SD — standard deviation.
Table 3. VRF_11 blood level in laboratory animals after intravenous administration at a dose of 250 mg/kg (n = 6, ng/ml)
Note: М — mean value for the time point; SD — standard deviation.
Table 4. Main pharmacokinetic parameters of VRF_11 (intravenous administration at a dose of 250 mg/kg )
Table 5. VRF_11 level (ng/g of tissue) in the cerebral cortex homogenate extracts after the single intravenous administration of the drug at a dose of 250 mg/kg
Note: М — mean value for the time point; SD — standard deviation.
Table 6. Ischemia focus volume, mm3 (M ± m; n = 8)
Note: М — mean value for the time point; SD — standard deviation; *— p < 0.05 (comparison of mean values within the same group in relation to the 1st day).
Table 7. Neurological deficit assessment using the mNSS scale (M ± m; n = 8)
Note: * — p < 0.05 (comparison of mean values within the same group in relation to the 1st day).
Table 8. Activity indicators in the open field test on the 16th day after reperfusion (M ± m; n = 8)
Note: * — p < 0.05 (comparison of mean values in relation to the control group).