Results of investigation of the analgesic activity of the natural recombinant peptide PT1, which specifically binds to P2X3 receptors, are presented. The test for hypersensitivity provoked by complete Freund’s adjuvant (CFA) showed evidence of the analgesic activity of PT1 peptide in CD-1 mice after single intravenous administration in a dose range of 0.01 – 1 mg/kg.

Проведено исследование влияния на поведение самцов мышей ICR новых потенциальных обезболивающих соединении пептидной (APCH3 и РТ1) и непептидной (севанол) природы. Все исследуемые вещества в тесте «открытое поле» не оказывали влияния на поведение мышей в дозах, вызывающих эффективную анальгезию. Однако APCH3 оказывает седативное действие на мышей в дозах, в 10000 раз превышающих фармакологически активную. Тогда как севанол в дозе в 35 мг/кг вызывал достоверное изменение поведения относительно фармакологически активной дозы 1 мг/кг, но не от контроля.

Представлены результаты исследования активности нового полипептидного модулятора TRPV1-рецепторов — АРНС2, выделенного из анемоны Heteractis crispa. Показано, что АРНС2 обладает анальгетическими свойствами, не нарушает нормальной двигательной активности и не изменяет температуру тела и гемостаз экспериментальных животных, что имеет большую практическую ценность для создания эффективных анальгетиков нового поколения. В исследовании гемодинамической активности наблюдается краткосрочное повышение ЧСС. Дальнейшее исследование особенностей связывания этого полипептида с рецептором TRPV1 может открыть подходы к созданию других антагонистов этого рецептора.

Показано, что полипептидные анальгетические соединения APCH3 (ингибитор TRPV1 рецептора) и РТ1 (ингибитор P2X3 рецептора) не оказывают действия на сердечно-сосудистую и дыхательную системы как при однократном, так и при многократном введении мышам. Низкомолекулярное вещество севанол (ингибитор ASIC3 рецепторов) не влияет на сердечно-сосудистой систему, однако при длительном применении в течение 14 дней влияет на параметры дыхательной системы, достоверно увеличивая частоту дыхания и максимальный поток выдоха.

The article describes the landmarks of control and licensing system development for the purpose of drug evaluation, marketing authorization and circulation in Russia. The need for the development of a state institution for performing expert evaluation of medicines was satisfied in 1990 by the establishment of the All-Soviet Union Scientific Centre for Expert Evaluation of Medicines (renamed in 1992 as the Russian State Centre for Expert Evaluation of Medicines - RSCEEM). The activities of the Centre included expert evaluation of all documents for new pharmaceutical products; organization and monitoring of clinical trials, as well as the assessment of their results; development of the recommendations regarding marketing authorization and medical use of new medicines. It also exercised the functions of the Federal Centre for Adverse Drug Reaction Study. RSCEEM became a basis for modern currently functioning Scientific Centre for Expert Evaluation of Medicinal Products».

The authors have analyzed international experience in creating legal documents regulating the use of animals for scientific purposes. Topical issues related to the use of laboratory animals for scientific purposes in the Russian Federation, including for the purpose of preclinical studies on the efficacy and safety of new medicines, are discussed. The negative effects of the lack a clear and consistent legal framework for the organization and limits of the use of laboratory animals for research purposes in the Russian Federation are identified. Particular attention is paid to the issue of bioethics, the principles of ethical expertise of research activities involving laboratory animals and the issues of bioethical committees activities. The basic directions of perfection of normative-legal acts and methodological documents in the field of organization and limits of the use of laboratory animals for research purposes are proposed.

Advanced therapy medicinal products (ATMP) represent a heterogeneous group of medicinal products, combined with the need for special regulation of their circulation. ATMP is a gene therapy medicinal products, a somatic cell therapy medicinal products, a tissue engineered products and combined ATMPs. The regulatory framework for ATMPs is established by Regulation (EC) No 1394/2007 on ATMPs which is designed to ensure the free movement of these medicines. The Committee for Advanced Therapies (CAT) of the European Medicines Agency (EMA) was established in accordance with the Advanced Therapies Regulation as a multidisciplinary committee, whose primary responsibility is to assess the quality, safety and efficacy of ATMPs, and to follow scientific developments in the field. Since June 2009 the CAT issues scientific recommendations on ATMPs classification. CAT defines the strategy for the identification and analysis of risks associated with the clinical application of ATMP and risk factors determined by the quality of the product and the ratio of benefit-risk. The article presents methods of analysis of risk factors in the study of ATMP.

The article presents generalized information about the program of the World Health Organization (WHO) related to International Nonproprietary Names (INN) of biological and biotechnological drugs. It reflects general principles for selecting INN for biological and biotechnological preparations, immunoglobulins (sera), preparations for gene therapy, glycosylated proteins and peptides, non-glycosylated proteins peptides and proteins, hybrid proteins, blood preparations, monoclonal antibodies, skin substitutes, transgenic products, vaccines, biosimilars. The conclusion was made about the need for an early solution to the global problem of assigning INN to biological and biotechnological drugs, while the number of authorized products remains relatively small.

Brief information about the program of the World Health Organization (WHO) for International Nonproprietary Names (INN) for drugs and the role of the INN in the sphere of circulation of medicines is represented. The general principles of INN selection and requirements for development applications for the INN are described. The assignment of an INN of the pharmaceutical substance is the highest criterion for recognition by the international expert community of innovative medicines created by a particular developer and makes it possible to objectively judge the contribution of different countries in global health. Questions of functioning of the national system of the selection and introduction of INN for domestic original pharmaceutical medicines have the high urgency.

One of the most promising trends of the modern medicine today gene therapy is considered to be the way of treatment of many diseases, including hereditary. However, global experience shows that the method is not absolutely safe. Several countries in Europe and other parts of the globe have already added gene therapy supplements to their gene engineering regulation. In the Russian Federation legal aspects of the research and application of gene medicines are much less developed. It is therefore important to develop the criteria for safety evaluation in the application of gene medicines and prepare guidelines for the public registration procedure.

The effect of an endotoxin from Sh. Boydii on the biotransformation of amidopyrine and acetanilide, the activity of microsomal monooxygenases, hemoxygenase, and xanthine oxidase, the lipid peroxidation (LPO) intensity, the phospholipid spectrum, and the solubilization of microsomal membrane components was studied by intraperitoneal injections (2.5 mg/kg) in rats. It was found that the endotoxin inhibits the reactions of C- and N-acetanilide hydroxylation, N-amidopyrine demethylation, acetanilide hydrolysis at the amide bond, conjugation of aminophenol metabolites with glucuronic acid and sulfate, and 4-aminoantipyrine binding to acetate. The endotoxin effect reached maximum 24 h after injection and was observed for 96 h. The inhibition of metabolism of the test preparations is related to a decrease in the content of cytochrome P-450 and in the activity of 1A2, its 2B, 2C, 3A, and 2E1 isoforms. This is obviously caused by activated LPO and enhanced nitric oxide synthesis, as evidenced by a tenfold increase in the content of NO metabolites (nitrites and nitrates) in the blood of test animals. In clinical practice, it is necessary to take into account the possibility of a significant biotransformation of drugs in the acute period of bacterial infection, which may lead to changes in the pharmacological effect and toxicity of some drugs.