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Pharmacokinetics and Pharmacodynamics

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No 2 (2020)
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FROM THE EDITOR

PRECLINICAL PHARMACODYNAMICS STUDIES

4-10 674
Abstract
In this work investigated the neuroprotective activity of analogues of substituted glyproline GZK-111 at the N-terminus in vitro. Oxidative stress caused by H2O2 (1.5 mM) led to significant decrease in the hippocampal cells HT-22 viability. The ethyl ester N-phenypropionyl-glycyl-proline (GZK-45) was effective at the concentrations up to 10–6 M in both experimental schemes. The compounds with N-acethyl (GZK-49) and N-capronoyl (GZK-46) fragments did not protective effect in both experimental schemes. GZK-45 also had protective effect in the 6-hydroxydopamine induced damage of SH-SY5Y neuroblastoma cells.
11-16 685
Abstract
The exprimants based on our translational model of chronic post-infarction heart failure within the use of echocardiography showed that in animals after 90 days after the reproduction of the myocardial infarction compared to the sham operated animals there is a significant increase in the endsystolic and end-diastolic sizes of the left ventricle (respectively, from 2.49 ± 0.09 to 3.91 ± 0.17 mm, p = 0.0002, and from 3.56 ± 0.12 to 5.20 ± 0.19 mm, p = 0.0002) and the decrease of its inotropic function that indicates a simulated pathology. 5 days after the echocardiographic study, the animals' exercise tolerance was assessed in the treadmill-run to failure test. It is proved in rats that 90 days after the coronary artery litigation the tolerance of physical activity decreases sharply – the value of the distance covered by them is 109.21 ± 11.61 m, which is 2.5 times less than the distance covered by sham operated animals (p = 0.003) and 5.3 times less than the distance covered by intact rats (p = 0.0001), – which is pathognomonic for chronic heart failure and complements the data of previously conducted morpho-histological, biochemical and molecular studies, indicating that the present model reproduces the main clinical and diagnostic signs of the simulated pathology.

PRECLINICAL PHARMACOKINETIC STUDIES

17-21 720
Abstract
The pharmacokinetics of the nerve growth factor mimetic GK-2 (dimeric dipeptide mimetic of the 4-th loop NGF, a derivative of fluoro-substituted 5-[2-(5-fluoropyrid-3-yl) -ethyl)]-2,8-dimethyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole) in rabbits after a single intravenous injection of an injectable dosage form at dose 24 mg (7,8-8,7 mg/kg). GK-2 concentrations in the blood plasma were determined by high-performance liquid chromatography with massspectrometric detection. GK-2 can be attributed to "short-lived" drugs, since the half-life from the rabbits blood plasma was 0.9±0.1 h.
22-27 767
Abstract
An experimental comparative study of the relative bioavailability of plant alkaloid harmine (native, in the form of a base) in comparison with its derivative harmine hydrochloride was carried out on chinchilla rabbit. Both substances was administered in capsules, containing an equimolar amount of harmine (50 mg, p.o.). Harmin hydrochloride was shown to have some pharmacokinetic advantages in comparison with native harmin due to a relatively rapid achievement of the maximal plasma concentration (Tmax) and a significantly higher maximum concentration of the active substance in the blood. At the same time, there was shown that the chemical modification of harmine does not significantly affect on such pharmacokinetics parameter as the area under the curve (AUC), which indicates the absence of a difference in the degree of absorption in the compared dosage forms.
28-33 802
Abstract
Performing pharmacokinetic and statistical analysis in the case of sparse data presents significant difficulties. Using the example of the pharmacokinetic (PK) study of resveratrol in mice, the resampling method was allowed us to obtain individual PK-parameters and perform full-fledged statistical tests.

TOXICOLOGY STUDY

34-36 593
Abstract
The study of allergenic properties and immunotoxic effects of the ready-to-use drug form of GML-1 (N-benzyl-N-methyl-1-phenylpyrrolo[1,2-a] pyrazin-3-carboxamide), compounds with high TSPO affinity and pronounced anxiolytic activity, was carried out. The study of allergenic properties and immunotoxicity of GML-1 was performed on male albino guinea pigs weighing 250-300 g and on male CBA, C57BL / 6, F1 hybrids (CBAxC57BL/6) mice. When assessing immunotoxicity, GML-1 was inject to mice per os for 14 days in doses of 2.2 mg / kg and 22 mg / kg. When studying the allergenicity, GML-1 was injected to albino guinea pigs in doses of 1 mg / kg and 10 mg / kg according to standard regimens of immunization. The results of the study of the immuno-toxicity and allergenicity of GML-1 allow us to conclude that the injection of tablet dosage form of GML-1 in the range of studied doses does not have an immunotoxic effect and allergenic properties.

CLINICAL STUDIES

37-41 621
Abstract
Relevance: the problem of cognitive violations at middle-aged persons with stenoziruyushchy atherosclerosis of brakhiotsefalny arteries and interrelation between the BDNF level and cognitive violation at this group of persons is considered. Materials and methods: 50 patients whose average age 52 years with displays of stenoziruyushchy atherosclerosis of brakhiotsefalny arteries took part in research. The control group included 50 people with average age of 50 years without symptoms of atherosclerosis of brakhiotsefalny arteries. To all patients neuropsychological testing and research of the BDNF level was conducted. Results: on the basis of our supervision, it is expedient to consider the revealed features of cognitive violations at patients of middle age, haemo dynamic characteristics, level of maintenance of BDNF in blood plasma at dodementny stages of tserebrovaskulyarny frustration at inspection and planning of approaches to treatment of patients with this pathology.
42-48 614
Abstract
Examination of healthy young volunteers of 22±1.4 years (n = 50) is conducted and levels of 48 microelements in hair are determined. It is shown that levels of a neurotrophic factor of a brain in a blood plasma are directly proportional to levels of lithium and copper in hair. Neurotropic effects of these microelements are considered.


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ISSN 2587-7836 (Print)
ISSN 2686-8830 (Online)