Vol 7, No 4 (2019)

Articles

ANALYTICAL FEATURES OF SYNTHETIC MDMB(N)-073F CANNABIMIMETICS AND ITS MARKERS IN BIOLOGICAL MATERIAL

Kataev S.S., Dvorskaya O.N., Gofenberg M.A., Labutin A.V., Melentyev A.B.

Abstract

The aim of the research is to study both analytical features of synthetic MDMB(N)-073F cannabimimetics of indazole carboxamides group by gas chromatography methods combined with tandem mass spectrometry (GC-MS) and high performance liquid chromatography with high-resolution mass spectrometry (HPLC-HRMS) as well as characteristics of the major MDMB(N)-073F metabolite, its glucuronide and derivatives, using gas chromatography with mass-spectrometric (GC-MS) detection and high-performance liquid chromatography (HPLC) with MS/MS mass spectrometry (HPLC-MS/MS) in urine samples to be applied in expert practice, chemical-toxicological and forensic and chemical analyses.Materials and methods. To carry out the study, the following materials were used: plant-based objects with narcotic drugs withdrawn from illegal trafficking and applied to them;. urine samples to be studied under chemical-toxicological and forensic and chemical analyses. For solid-phase epitaxy, SampliQ EVIDEX TFE cartridges - 200 mg - 3 ml (Agilent, USA) were used for sample preparation; β-glucuronidase, Type HP-2, From Helix Pomatia, 100000 UA/ml (Sigma-ALDRICH CHEMI, Germany) was used for enzymatic hydrolysis. GC-MS/MS analysis was made using Agilent 7890 gas chromatograph with a tandem quadrupolar mass-spectrometer Agilent 7000 (Agilent, США); GC-MS analysis was carrid out using gas chromatograph Agilent 7820 with mass-selective detector Agilent 5975 (Agilent, USA); HPLC-HRMS research was made on liquid chromatograph Agilent 1260 with tandem hybrid high-resolution quadrupole-time-of-flight detector Agilent 6540 (Agilent, США); liquid chromatograph Agilent 1260 with Agilent 6460 (Agilent, USA) with tandem mass-spectrometer were used for making HPLC-MS/MS research.Results. The structure of MDMB(N)-073F compound has been confirmed and an exact mass of the protonated molecule corresponding to the chemical formula C19H27FN3O3 fixed by GC-MS/MS and HPLC-HRMS methods. Spectral characteristics of MDMB(N)-073F have been given. One of the branches in MDMB(N)-073F biotransformation in the human body found out by GC-MS and HPLC-MS/MS methods, is the ester decomposition with further conjugation of the resulting acid. The product interacting with glucuronic acid, is found to be the conjugate of major MDMB(N)-073F metabolite of the Ist phase in biotransformation. Metabolites appearing due to the ester decomposition and its conjugate with glucuronic acid, are recommended to be used as markers for synthetic MDMB(N)-073F cannabimimetics in the analysis by chromatographic methods; they can be used for regular screening of biological samples.Conclusion. The research results presented here, are the following: the analytical features characteristic for synthetic MDMB(N)-073F cannabimimetics found out by gas chromatography methods combined with tandem mass spectrometry (GC-MS/ MS) and liquid chromatography of hybrid high-resolution quadrupole-time-of-flight mass spectrometry (HPLC-HRMS), as well as characteristics of major MDMB(N)-073F metabolite, its glucuronide and derivatives with the use of gas chromatography with mass-spectrometric detection (GC-MS) and liquid chromatography combined with tandem mass spectrometry (HPLC-MS/MS) in urine samples to be applied in expert practice, chemical-toxicological, forensic and chemical analyses.
Pharmacy & Pharmacology. 2019;7(4):184-197
pages 184-197 views

EFFECT OF PUMPKIN (CUCURBITA PEPO L.) AND MARIGOLD (TAGETES PATULA L.) EXTRACTS ON HIPPOCAMPAL MITOCHONDRIA FUNCTIONAL ACTIVITY WITHIN CONDITIONS OF EXPERIMENTAL ACUTE BRAIN HYPOMETABOLISM

Voronkov A.V., Pozdnyakov D.I., Adzhiakhmetova S.L., Chervonnaya N.M., Miroshnichenko K.A., Sosnovskaya A.V., Chereshkova E.I.

Abstract

The aim of the study is to evaluate the effect of pumpkin (Cucurbita pepo L.) and marigold extracts (Tagetes patula L.) on the hippocampal mitochondria functional activity within the conditions of experimental acute brain hypometabolism.Materials and methods. The work was performed on 50 male Wistar rats, which reproduced an acute brain hypometabolic state by administration of a 3M sodium azide solution in hippocampus (n = 40 and n = 10 - a group of sham-operated animals). The test extracts and the reference drug - EGb 761 - were prophylactically administered at the dose of 100 mg/kg per os for 10 days. 24 hours after the last administration, sodium azide was injected, the brain was taken, the hippocampus was isolated to obtain a supernatant and determine the parameters of mitochondrial respiration, the intensity of anaerobic processes, the concentration of the apoptosis-inducing factor, endonuclease G, and β-amyloid.Results. The carried out study established that the prophylactic administration of pumpkin and marigold extracts contributed to the restoration of a mitochondrial function and a decrease in the intensity of anaerobic processes. In the group of the rats treated with pumpkin and marigold extracts, an increase of ATP concentration in the hippocampal supernatant by 65.7% (p<0.002) was observed; it was 66.2% (p><0.002) relative to the animals deprived of pharmacological support. ,When the rats were treated with pumpkin and marigold extracts, a decrease in the concentration of apoptosis-inducing factor (by 33% (p><0.002) and 38.3% (p><0.002), respectively) and endonuclease G (by 3.6 times (p><0.002) and 4.4 times (p><0.002), respectively) was also noted. The administration of pumpkin and marigold extracts reduced the amyloid β-peptide concentration in the rats’ hippocampus by 54.4% (p><0.0002) and 54.4% (p><0.0002), respectively. The test-extracts had an equivalent therapeutic efficacy with the reference drug. Conclusion On the basis of the obtained data, it is possible to suggest the prospect of a further study of pumpkin and marigold extracts as the drugs of a targeted correction of cerebral hypometabolism. Keywords: plant extracts, hypometabolism, hippocampus, mitochondria >< 0.002) was observed; it was 66.2% (p<0.002) relative to the animals deprived of pharmacological support. ,When the rats were treated with pumpkin and marigold extracts, a decrease in the concentration of apoptosis-inducing factor (by 33% (p><0.002) and 38.3% (p><0.002), respectively) and endonuclease G (by 3.6 times (p><0.002) and 4.4 times (p><0.002), respectively) was also noted. The adm>< 0.002) relative to the animals deprived of pharmacological support. ,When the rats were treated with pumpkin and marigold extracts, a decrease in the concentration of apoptosis-inducing factor (by 33% (p<0.002) and 38.3% (p><0.002), respectively) and endonuclease G (by 3.6 times (p><0.002) and 4.4 times (p><0.002), respectively) was also noted. The administration of pumpki>< 0.002) and 38.3% (p<0.002), respectively) and endonuclease G (by 3.6 times (p><0.002) and 4.4 times (p><0.002), respectively) was also noted. The administration of pumpkin and marigold extracts reduced the amyloid β-peptide concentration in the rats’ hippocampus by 54.4% (p><0.0002) and 54.4% (p><0.0002), respectively. The test-extracts had an equivalent therapeutic efficacy with >< 0.002), respectively) and endonuclease G (by 3.6 times (p<0.002) and 4.4 times (p><0.002), respectively) was also noted. The administration of pumpkin and marigold extracts reduced the amyloid β-peptide concentration in the rats’ hippocampus by 54.4% (p><0.0002< 0.002) and 4.4 times (p<0.002), respectively) was also noted. The administration of pumpkin and marigold extracts reduced the amyloid β-peptide concentration in the rats’ hippocampus by 54.4% (p><0.0002) and 54.4% (p><0.0002), respectively. The te>< 0.002), respectively) was also noted. The administration of pumpkin and marigold extracts reduced the amyloid β-peptide concentration in the rats’ hippocampus by 54.4% (p<0.0002) and 54.4% (p><0.0002), respectively. The test-extracts had an equiva>< 0.0002) and 54.4% (p<0.0002), respectively. The test-extracts had an equivalent therapeutic efficacy with the reference drug. Conclusion On the basis of the obtained d>< 0.0002), respectively. The test-extracts had an equivalent therapeutic efficacy with the reference drug.Conclusion On the basis of the obtained data, it is possible to suggest the prospect of a further study of pumpkin and marigold extracts as the drugs of a targeted correction of cerebral hypometabolism.
Pharmacy & Pharmacology. 2019;7(4):198-207
pages 198-207 views

INFLUENCE OF HEPARINOID FROM PAEONIA LACTIFLORA ON HEMOSTATIC SYSTEM WITHIN CONDITIONS OF PRETHROMBOSIS

Lyapina M.G., Uspenkaya M.S., Maistrenko E.S., Kalugina M.D.

Abstract

The search and development of direct and rapid anticoagulants used per os, is an urgent problem in physiological and medical science. A number of plants contain heparin-like components with a positive effect on the hemostatic system, both within normal and in some pathological conditions of the body.The aim of the work was to study the complex effect of fibrin, a heparin-like substance (heparinoid) from the roots of Paeonia lactiflora, on fibrinolytic, anticoagulant systems of the body and polymerization processes, when it is administered per os in animals within normal conditions and when modeling the state of prethrombosis.Materials and methods. To carry out the research, the roots of Paeonia lactiflora growing in the Botanical Garden of Moscow State University, and laboratory animals - male Wistar rats - were used. To study the antithrombotic effects of the extract from roots containing heparinoid, the state of prethrombosis was modeled in rats. The determined parameters of hemostasis were: anticoagulant activity according to the tests of activated partial thromboplastin time and thrombin time, fibrinolytic activity according to the test of total fibrinolytic activity, fibrin polymerization according to the test of fibrindepolymerization activity of blood plasma.Results. With repeated (every 24 hours within 3 days) oral administration of the extract containing heparinoid, in animals within normal conditions and with prethrombosis, the following anticoagulant effects were established in the blood: an increase in anticoagulant, fibrindepolymerization and fibrinolytic plasma activity. Possible mechanisms of the activating effect of heparinoid on fibrinolysis and anticoagulant properties of plasma due to the excretion of tissue plasminogen activator into the bloodstream from the endothelium, thrombin inhibition, and fibrin polymerization are described. Moreover, the anticoagulant effect of the use of the extract from the peony roots was equivalent to that of the reference drug of low molecular weight heparin from Celsus (USA). For the first time, it was revealed that when modeling experimental prethrombosis, the administration of heparinoid in rats at the dose of 37.5 IU/kg МЕ/кг body weight restored impaired hemostasis, which requires a further study.Conclusion. The ability of heparinoid from peony roots to normalize the functional state of the anticoagulant system during the development of prethrombosis in animals has been established. The restriction of fibrin polymerization during oral administration of heparinoid from peony in animals by increasing the enzymatic fibrinolytic and fibrindepolymerization activity of blood plasma was revealed. In the future, heparinoid can be used as an antithrombotic agent.
Pharmacy & Pharmacology. 2019;7(4):208-214
pages 208-214 views

APPLICATION OF DRUG-RELATED PROBLEMS APPROACH TO ANALYSIS OF NON-STEROIDAL ANTI-INFLAMMATORY DRUGS’ SAFETY

Matveev A.V., Krasheninnikov A.E., Egorova E.A., Konyaeva E.I.

Abstract

A Drug-Related Problem is an event or circumstance involving drug therapy that actually or potentially interferes with desired health outcomes.The aim of the study was the analysis of the adverse drug reactions (ADR) associated with prescription of the non-steroidal anti-inflammatory drugs (NSAIDs) using the DRP PCNE V5.01 qualification system.Materials and methods. The objects of the study were 415 notification forms about adverse drug reactions of NSAIDs recorded in the regional database of spontaneous reports and called ARCADe (Adverse Reactions in Crimea, Autonomic Database) for the period from 1 January 2009 to 31 December of 2018. The study and analysis of the problems associated with drugs were carried out using the qualification system DRP PCNE V5.01 (Pharmaceutical Care Network Europe) 2006 in the modification of Prof. Zimenkovsky.Results. Among other representatives of the NSAID group, Ibuprofen and Diclofenac became the “leaders” in the incidence of ADR. The frequency of ADR cases for Ibuprofen was 142 reports (34.22% of the total number of ADR for NSAIDs), and for Diclofenac it was 90 cases (21.69%). The calculation of DRP values for each of the presented cases made it possible to determine that in 81 (19.51%) and 91 (21.9%) cases, the DRP value was 6 and 7, respectively. DRP values in the range of 8-10 were found in 92 reports. The highest DRPs value was observed after the administration of Parecoxib (13 problems but only one case was found in the database), the DRPs value of Dexketoprofen was 12.5 (95% CI: 7-17) and the DRPs value of Diclofenac combinations was 10 DRPs; 95% CI: 5-17 DRP). The minimum DRPs values were associated with Naproxen, Rofecoxib, and Etoricoxib prescriptions.Conclusion. Using the DRP system in the analysis of NSAIDs, ADRs allow to identify the medicines which have a high risk of causing safety problems, such as Parecoxib, Dexketoprofen and Diclofenac combinations. The prescription of these drugs should be carried out with special cautions and control to the indications and contraindications, the dose and duration of treatment, as well as to a possible interaction of them with concomitant drugs.
Pharmacy & Pharmacology. 2019;7(4):215-223
pages 215-223 views

GLYPROLINES AS MODULATORS OF IMMUNOREACTIVITY WITHIN CONDITIONS OF “SOCIAL” STRESS

Samotrueva M.A., Yasenyavskaya A.L., Bashkina O.A., Myasoedov N.F., Andreeva L.A.

Abstract

The most important direction in the development of modern medical science is the study of protective, compensatory and pathological reactions of the organism that occur in response to various stress factors.The aim of the study is the subsequent development of methods for pharmacological correction of these reactions. The remedies for the correction of stress-induced immunity disorders are represented by the glyprolin group - the Selank drug and the Pro-Gly-Pro peptide compound - and are of particular interest. The aim of the experiment was to study the immunomodulating effect of glyprolines on the basis of the “social stress” model.Materials and methods. The experiment was performed on non-linear male rats aged 6-8 months. A model of a sensor contact was used as a model of the experimental “social stress”. The animals were divided into groups (n = 10): a “control” group was represented by individuals with aggressive and submissive types of behavior, formed within the conditions of the experimental “social stress” for 20 days; and 2 experimental groups in which the animals were intraperitoneally administered Selank (100 µg/kg) and Pro-Gly-Pro (100 µg/kg) against the background of the experimental “social” stress once a day for 20 days. A functional activity of the immune system was studied on the basis of standard immunopharmacological tests: a delayed-type hypersensitivity test (DTH test), a direct agglutination test (DAT), a latex test for studying the Neutrophil phagocytic rate of peripheral blood, and the essessment of the leucogram.Results. It has been established, that within the conditions of the “social” stress, the changes in the immune response are multidirectional. That fact confirms the theory of “the immune disbalance” caused by the action of stressors. As a result of studying the effect of glyprolines within the conditions of “the social stress”, Selank and Pro-Gly-Pro proved to be effective immunocorrectors, restoring cellular and humoral immunogenesis reactions as well as the phagocytic activity of neutrophils and leucogram indices.Сonclusion. The carried out study expands understanding of the immunoreaction pathogenesis within the stress-induced conditions in order to further develop a pharmacological strategy for correcting the revealed disorders through the substances of the neuropeptide structure.
Pharmacy & Pharmacology. 2019;7(4):224-230
pages 224-230 views

STUDY OF ANTISECRETORY ACTIVITY OF DINITRATE 2-PHENYL-9-DIETHYLAMINOETHYLimidazo[1,2-A] BENZIMIDAZOLE BY METHOD OF CONTINUOUS PERFUSION OF RATS’ STOMACHS

Chernikov M.V., Oganova M.A., Gerasimenko A.S., Artemyev E.A.

Abstract

Nowadays, effective pharmacotherapy of acid-dependent gastrointestinal diseases remains an urgent problem of modern gastroenterology. In this regard, the search for new drugs with a pronounced antisecretory activity still continues; their aim is to keep the control over the acid production safe and effective.The aim of this study was an experimental study of the antisecretory activity of the substance and the finished dosage form (FDF) of dinitrate 2-phenyl-9-diethylaminoethylimidazo[1,2-a]benzimidazole.Materials and Methods. The study of antisecretory activity was performed by method of a continuous perfusion of rats’ stomachs. The studied substance was administered at the doses of 3, 10 and 30 mg/kg, and the FDF - at the doses of 13 and 26 mg/kg. The substance of Ranitidine (Sigma Аldrich, USA) was used as a reference object in the study of the antisecretory activity of the substance under study, and Ranitidine (Hemofarm A.D., Serbia) was used as a reference drug in the study of the FDF. In order to determine the stimulated secretion immediately before collecting the samples of the perfusate, histamine was administered subcutaneously at the dose of 5 mg/kg. The content of hydrochloric acid in the perfusate was determined by titration of a 0.01 M sodium hydroxide solution. The acidity value was determined in terms of the debit-hour of hydrochloric acid.Results and discussion. The obtained experimental data showed that the studied substance at the dose of 30 mg/kg decreased the basal hydrochloric acid secretion by 54%, which significantly exceeded the antisecretory effect of Ranitidine by 1.8 times. The FDF at the dose of 26 mg/kg, statistically reliable relative to the control and the group treated with Ranitidine, decreased the basal secretion of gastric juice by 33%. The substance at the dose of 30 mg/kg reliably suppressed the stimulated secretion of hydrochloric acid by 80%, while Ranitidine did it by 56%. The FDF at the dose of 26 mg/kg decreased the histamine-stimulated secretion by 66%, and Ranitidine did it by 52%, which was statistically reliable.Сonclusions. The studied substance and its dosage form are more effective in suppressing basal activities and exceed the anisecretory activity of H2 -histamine antagonists of Ranitidine under the conditions of the secretion stimulated by histamine.
Pharmacy & Pharmacology. 2019;7(4):231-240
pages 231-240 views

This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies