farmaecFARMAKOEKONOMIKA. Modern Pharmacoeconomics and PharmacoepidemiologyФАРМАКОЭКОНОМИКА. Современная фармакоэкономика и фармакоэпидемиология2070-49092070-4933IRBIS LLC10.17749/2070-4909/farmakoekonomika.2024.260farmaec-1033Research ArticleORIGINAL ARTICLESОРИГИНАЛЬНЫЕ ПУБЛИКАЦИИChemoreactomic study of fonturacetam effects: molecular mechanisms of influence on adipose tissue metabolismХемореактомное исследование эффектов препарата Актитропил (фонтурацетам): молекулярные механизмы влияния на метаболизм жировой тканиhttps://orcid.org/0000-0002-7663-710XГромоваО. А.GromovaO. A.

Громова Ольга Алексеевна – д.м.н., профессор, ведущий научный сотрудник

WoS ResearcherID: J-4946-2017

 Scopus Author ID: 7003589812

ул. Вавилова, д. 44, корп. 2, Москва 119333

Olga A. Gromova – Dr. Med. Sc., Professor, Leading Researcher

WoS ResearcherID: J-4946-2017

Scopus Author ID: 7003589812

44 corp. 2 Vavilov Str., Moscow 119333

unesco.gromova@gmail.comhttps://orcid.org/0000-0002-2659-7998ТоршинИ. Ю.TorshinI. Yu.

Торшин Иван Юрьевич – к.ф-м.н., к.х.н., ведущий научный сотрудник

WoS ResearcherID: C-7683-2018

Scopus Author ID: 7003300274

ул. Вавилова, д. 44, корп. 2, Москва 119333

Ivan Yu. Torshin – PhD (Phys. Math.), PhD (Chem.), Leading Researcher

WoS ResearcherID: C-7683-2018

Scopus Author ID: 7003300274

44 corp. 2 Vavilov Str., Moscow 119333

Федеральный исследовательский центр «Информатика и управление» Российской академии наукРоссияFederal Research Center “Computer Science and Control”, Russian Academy of SciencesRussian Federation202403082024172172181Copyright © Gromova O.A., Torshin I.Y., 20242024Громова О.А., Торшин И.Ю.Gromova O.A., Torshin I.Y.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.pharmacoeconomics.ru/jour/article/view/1033Objective

Objective: to conduct chemoreactomic, pharmacoinformatic and chemoneurocytological analyzes of the properties of racetams (piracetam, aniracetam, pramiracetam, levetiracetam, fonturacetam).

Material and methods

Material and methods. Chemoreactomic, pharmacoinformatic and chemoneurocytological methods of molecule properties analyzis are based on chemoreactomic methodology – the latest direction in the application of machine learning systems in the field of postgenomic pharmacology. Analysis of pharmacological capabilities of molecules within the framework of chemoreactomic methodology is carried out by comparing the chemical structure of racetam molecules with the structures of molecules for which pharmacological properties were studied using training artificial intelligence algorithms based on big data information presented in PubChem, HMDB, STRING, PharmGKB databases. Based on the entire complex of differences between molecules in interactions with receptor proteins, an “anti-obesity” score was calculated for each one as a serial number of this molecule in descending order by corresponding IC50, EC50 chemoreactomic constants values.

Results

Results. The lipolytic effect is predicted specifically for fonturacetam as a result of activation by this molecule of β3-adrenoceptors, adenosine receptors, glucagon-like peptide, sphingosine phosphate and peroxisome proliferators, as well as specific inhibition of cannabinoid, opioid, histamine, glutamate, nociceptin, orexin and neuropeptide Y receptors. Due to these mechanisms fonturacetam will contribute to normalizing appetite and improving adipose tissue metabolism. The total lipolytic effect score was calculated for all established interactions with receptors and amounted to 4.3±0.9 for fonturacetam, 3.0±1.4 for pramiracetam, and 2.5±1.5 for all other molecules.

Conclusion

Conclusion. The results of the analysis suggest that the lipolytic effects of fonturacetam (Actitropil – Pharmstandard, Russia) will be much stronger than for other racetams (piracetam, aniracetam, pramiracetam, levetiracetam). Chemoreactomic analysis of fonturacetam indicated new mechanisms of pharmacological action of the molecule, providing a decrease in excess appetite and body weight normalization. Fonturacetam is the only nootropic drug indicated for the treatment of obesity.

Цель

Цель: провести хемореактомный, фармакоинформационный и хемонейроцитологический анализ свойств рацетамов (пирацетам, анирацетам, прамирацетам, леветирацетам, фонтурацетам).

Материал и методы

Материал и методы. Хемореактомный, фармакоинформационный и хемонейроцитологический методы анализа свойств молекул основаны на хемореактомной методологии – новейшем направлении приложения систем машинного обучения в области постгеномной фармакологии. Оценка фармакологических возможностей молекул в рамках хемореактомной методологии проводится посредством сравнения химической структуры молекул рацетамов со структурами молекул, для которых молекулярно-фармакологические свойства изучены с использованием алгоритмов обучения искусственного интеллекта на основе информации типа big data, представленной в базах данных PubChem, HMDB, STRING, PharmGKB. На основании всего комплекса различий между молекулами во взаимодействиях с белками-рецепторами для каждой вычисляли балл «противодействия ожирению» как порядковый номер этой молекулы при упорядочении по убыванию значений соответствующих хемореактомных констант IC50, EC50.

Результаты

Результаты. Липолитический эффект прогнозируется именно для фонтурацетама в результате активации этой молекулой β3-адреноцепторов, рецепторов аденозина, глюкагоноподобного пептида, сфингозинфосфата и пролифераторов пероксисом, а также специфического ингибирования каннабиноидных, опиоидных, гистаминовых, глутаматных, ноцицептиновых, орексиновых рецепторов и рецепторов нейропептида Y. Вследствие действия этих механизмов фонтурацетам будет способствовать нормализации аппетита и улучшению метаболизма жировой ткани. Значения суммарного балла липолитического эффекта, полученные по всем установленным взаимодействиям с рецепторами, составили 4,3±0,9 для фонтурацетама, 3,0±1,4 для прамирацетама и 2,5±1,5 для всех остальных молекул.

Заключение

Заключение. Результаты анализа позволяют утверждать, что липолитические эффекты фонтурацетама (Актитропил – АО «Фармстандарт», Россия) будут проявляться гораздо сильнее, чем для других рацетамов (пирацетама, анирацетама, прамирацетама, леветирацетама). Хемореактомный анализ фонтурацетама указал на новые молекулярные механизмы фармакологического действия молекулы, обеспечивающие снижение избыточного аппетита и нормализацию массы тела. Фонтурацетам является единственным ноотропным препаратом, показанным для терапии ожирения.

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The authors declare that there are no conflicts of interest present.