mrjСовременная ревматологияModern Rheumatology Journal1996-70122310-158XIMA-PRESS, LLC10.14412/1996-7012-2014-2-83-89mrj-540Research ArticleОБЗОРЫREVIEWSНа пути к созданию новой генерации нестероидных противовоспалительных препаратов: амтолметин гуацилOn the way toward designing next-generation nonsteroidal anti-inflammatory drugs: amtolmetin guacilКаратеевА.Е.KarateevA.E.1@ru.ruФГБУ «Научно-исследовательский институт ревматологии им. В.А. Насоновой» РАМН, Москва, РоссияV.A. Nasonova Research Institute of Rheumatology, Russian Academy of Medical Sciences, Moscow, Russia201408052014828389Copyright © Каратеев А., 20142014Каратеев А.Karateev A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://mrj.ima-press.net/mrj/article/view/540

Нестероидные противовоспалительные препараты (НПВП) – основное средство симптоматической терапии при ревматических заболеваниях, их использование позволяет уменьшить выраженность наиболее неприятных проявлений болезни и улучшить качество жизни пациентов. К сожалению, возможности терапии НПВП ограничивает риск развития опасных осложнений со стороны желудочно-кишечного тракта (ЖКТ) и сердечно-сосудистой системы. До настоящего времени во всем мире продолжается работа по созданию новых, более безопасных представителей этой лекарственной группы. К таким препарата можно отнести коксибы (высокоселективные ингибиторы циклооксигеназы – ЦОГ – 2), комбинированные препараты, содержащие НПВП и гастропротекторы (мизопростол, Н2-блокаторы, ингибиторы протонной помпы), ингибиторы ЦОГ2/ЛОГ2 (липооксигеназы 2), а также донаторы оксида азота – NO (CINOD). Однако все эти препараты, как оказалось, имеют серьезные недостатки. Часть из них активно применяются, продвижение некоторых остановлено на уровне клинических испытаний, другие перестали использоваться из-за неудачного соотношения эффективности и переносимости. Новый представитель «улучшенных» НПВП амтолметин гуацил (АМГ) синтезирован на основе неселективного НПВП толметина; от своего предшественника он отличается комплексом гастропротективных свойств, главным из которых является повышение концентрации NO в слизистой оболочке ЖКТ. Рассматриваются фармакологические особенности АМГ, представлены данные его лабораторных и клинических испытаний. 

Nonsteroidal anti-inflammatory drugs (NSAIDs) are the main component of symptomatic treatment of patients with rheumatic disorders. The use of these drugs reduces the intensity of the most unpleasant symptoms and improves patients’ quality of life. Unfortunately, NSAID therapy is limited by the risk of dangerous gastric and cardiovascular complications. Researchers all over the world are involved in designing new drugs belonging to this family that would be characterized by increased safety. These drugs include coxibs (selective cyclooxygenase-2 (COX-2) inhibitors), combination drugs containing NSAIDs and gastroprotector agents (misoprostol, H2 blockers, proton pump inhibitors), COX2/LOG2 (lipoxygenase 2) inhibitors, and COX-inhibiting nitric oxide donors (CINODs). However, all these drugs proved to have serious drawbacks. Some of them are being actively used; launching of other drugs has been stopped at the stage of clinical trials; while the others were abandoned because of inadequate efficacy/tolerability ratio. A new representative of improved NSAIDs, amtolmetin guacil (AMG), was synthesized from tolmetin, a nonselective NSAID. As opposed to tolmetin, AMG has a number of gastroprotective properties. The most important one is that it increases NO concentration in the mucous membrane of the gastrointestinal tract. The pharmacological features of AMG are discussed; the data obtained during pre-clinical and clinical trials are reported. 

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