Molekulyarnaya Meditsina (Molecular medicine)Molekulyarnaya Meditsina (Molecular medicine)Молекулярная медицина1728-29182499-9490Russkiy Vrach Publishing House68902010.29296/24999490-2025-03-03ReviewsОбзорыReview ArticleMolecular mechanisms and pharmacogenetic determinants of II–III generation antihistamines efficacy in allergic bronchial asthma: personalized therapy prospectsМолекулярные механизмы и фармакогенетические детерминанты эффективности антигистаминных препаратов II–III поколений при аллергической бронхиальной астме: перспективы персонализированной терапииhttps://orcid.org/0000-0002-3063-1538BorodulinaElena A.БородулинаЕлена Александровна
Russian Federation

Doctor of Medical Sciences, Professor, Head of the Department of Phthisiology and Pulmonology

доктор медицинских наук, профессор, заведующая кафедрой фтизиатрии и пульмонологии

borodulinbe@yandex.ruhttps://orcid.org/0000-0003-1858-5206YakovlevaElena V.ЯковлеваЕлена Вадимовна
Russian Federation

Candidate of Medical Sciences, Assistant of the Department of Phthisiology and Pulmonology

кандидат медицинских наук, ассистент кафедры фтизиатрии и пульмонологии

elena130894@mail.ruhttps://orcid.org/0000-0002-8847-9831BorodulinBoris E.БородулинБорис Евгеньевич
Russian Federation

Doctor of Medical Sciences, Professor; Professor of the Department of Phthisiology and Pulmonology

доктор медицинских наук, профессор, профессор кафедры фтизиатрии и пульмонологии

borodulinbe@yandex.ruhttps://orcid.org/0000-0002-8137-7197GladunovaElena P.ГладуноваЕлена Павловна
Russian Federation

Doctor of Pharmaceutical Sciences, Professor; Professor of the Department of Pharmacy Management and Economics

доктор фармацевтических наук, профессор, профессор кафедры управления и экономики фармации

e.p.gladunova@samsmu.ruhttps://orcid.org/0000-0002-0177-6826MarchenkoSevara D.МарченкоСевара Джурабековна
Russian Federation

Candidate of Pharmaceutical Sciences, Associate Professor of the Department of Organization and Management in the Field of Drug Circulation, Institute of Professional Education

кандидат фармацевтических наук, доцент кафедры организации и управления в сфере обращения лекарственных средств ИПО

marchenko_s_d@staff.sechenov.ruhttps://orcid.org/0000-0002-0552-639XKrylovaOlga V.КрыловаОльга Валерьевна
Russian Federation

Candidate of Pharmaceutical Sciences, Associate Professor of the Department of Pharmacy, A.P. Nelyubin Institute of Pharmacy

кандидат фармацевтических наук, доцент кафедры фармации Института Фармации им. А.П. Нелюбина

krylova_o_v@staff.sechenov.ruhttps://orcid.org/0000-0001-8199-2053MamontovaElza R.МамонтоваЭльза Руслановна
Russian Federation

Candidate of Pedagogical Sciences, Associate Professor of the Department of Pharmacy, Institute of Pharmacy and Medical Chemistry

кандидат педагогических наук, доцент кафедры фармации Института фармации и медицинской химии

elza.mamontova@mail.ruhttps://orcid.org/0009-0008-7211-4134RekaloAnastasia R.РекалоАнастасия Романовна
Russian Federation

5th year student

студентка V курса

rekalonastya@gmail.comhttps://orcid.org/0009-0006-7867-4461MinnullinaZarina R.МиннуллинаЗарина Руслановна
Russian Federation

6th year student

студентка VI курса

zarinam93@mail.ruhttps://orcid.org/0009-0008-0627-5167BagirovaBella R.БагироваБэлла Руслановна
Russian Federation

6th year student, Medical Institute

студентка VI курса, Медицинский институт

gm2112@mail.ruhttps://orcid.org/0009-0000-8946-612XSalpagarovaAlana A.СалпагароваАлана Алексеевна
Russian Federation

6th year student, Medical Institute

студентка VI курса, Медицинский институт

alanasalpagarova3@gmail.ruFederal State Budgetary Educational Institution of Higher Education “Samara State Medical University” of the Ministry of Healthcare of the Russian FederationФГБОУ ВО «Самарский государственный медицинский университет» Минздрава РоссииFederal State Autonomous Educational Institution of Higher Education I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University)ФГАОУ ВО Первый Московский государственный медицинский университет имени И.М. Сеченова Минздрава России (Сеченовский Университет)Federal State Autonomous Educational Institution of Higher Education “Russian National Research Medical University named after N.I. Pirogov” of the Ministry of Health of the Russian FederationФГАОУ ВО «Российский национальный исследовательский медицинский университет им. Н.И. Пирогова» Минздрава РоссииFederal State Budgetary Educational Institution of Higher Education “North Caucasian State Academy”ФГБОУ ВО «Северо-Кавказская государственная академия» Минобрнауки России2208202523319291108202511082025Copyright ©; 2025, Russkiy Vrach Publishing HouseCopyright ©; 2025, ИД "Русский врач"2025Russkiy Vrach Publishing HouseИД "Русский врач"https://journals.eco-vector.com/1728-2918/article/view/689020

Introduction. Allergic bronchial asthma (BA) is accompanied by activation of histamine H1/H4 receptors and variable response to antihistamines.

The aim of this review is to analyze the molecular mechanisms of action of second- and third-generation antihistamine drugs, their pharmacokinetic features and pharmacogenetic aspects of application in bronchial asthma, as well as prospects for developing new drugs with improved characteristics.

Methods. Narrative review of the literature (PubMed/Scopus, 2019–2024), including data from cryo-EM structures of the H4 receptor, single-cell RNA-seq profiles of bronchial epithelium and clinical pharmacogenetic studies of the CYP family (41 sources).

Results. Key signaling pathways (FcεRI–MAPK/NF-κB, IL-13/STAT6) indirectly targeted by H1 blockers have been identified. Increased HRH4 expression in IL-13^high Th2 clusters has been shown to correlate with asthma severity. Modern cryo-EM models of H4R have allowed us to refine the architecture of binding sites and optimize the design of promising ligands. CYP2D6 and ABCB1 polymorphisms account for up to 30–50% of interindividual variability in plasma concentrations of loratadine/desloratadine and bilastine according to clinical cohort data.

Conclusion. Integration of omics data and pharmacogenetic testing opens the way to targeted and personalized asthma therapy with antihistamines.

Введение. Аллергическая бронхиальная астма (БА) сопровождается активацией гистаминовых H1/H4-рецепторов и вариабельным ответом на антигистаминные препараты.

Целью настоящего обзора является анализ молекулярных механизмов действия антигистаминных препаратов II и III поколений, их фармакокинетических особенностей и фармакогенетических аспектов применения при БА, а также перспектив создания новых препаратов с улучшенными характеристиками.

Методы. Нарративный обзор литературы (PubMed/Scopus, 2019–2024 гг.), включающий данные cryo-EM-структур H4-рецептора, single-cell RNA-seq-профили бронхиального эпителия и клинические фармакогенетические исследования CYP-семейства (41 источник).

Результаты. Выявлены ключевые сигнальные пути (FcεRI–MAPK/NF-κB, IL-13/STAT6), мишенью которых опосредованно выступают Н1-блокаторы. Показано, что повышенная экспрессия HRH4 в IL-13^high Th2-кластерах может коррелировать с тяжестью БА. Современные cryo-EM-модели H4R позволили уточнить архитектуру сайтов связывания и оптимизировать дизайн перспективных лигандов. Полиморфизмы CYP2D6 и ABCB1 обусловливают до 30–50 % межиндивидуальной вариабельности плазменных концентраций лоратадина/деслоратадина и биластина согласно данным клинических когорт.

Заключение. Интеграция омикс-данных и фармакогенетического тестирования открывает путь к таргетной и персонализированной терапии БА антигистаминными препаратами.

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