safetyriskБезопасность и риск фармакотерапииSafety and Risk of Pharmacotherapy2312-78212619-1164Federal State Budgetary Institution ‘Scientific Centre for Expert Evaluation of Medicinal Products’ of the Ministry of Health of the Russian Federation (FSBI ‘SCEEMP’)safetyrisk-314Research ArticleОБЗОРЫ И ОРИГИНАЛЬНЫЕ СТАТЬИREVIEWS AND ORIGINAL ARTICLESИНВЕРСИРОВАННЫЕ АГОНИСТЫ: БОЛЬШЕ, ЧЕМ АНТАГОНИСТЫ?INVERSE AGONISTS: MORE THAN JUST ANTAGONISTS?АляутдинР. Н.AlyautdinR. N.РомановБ. К.RomanovB. K.Федеральное государственное бюджетное учреждение «Научный центр экспертизы средств медицинского применения» Министерства здравоохранения Российской Федерации, МоскваРоссияScientific Centre for Expert Evaluation of Medicinal Products Russian FederationRussian Federation20140206202204611Copyright © Аляутдин Р.Н., Романов Б.К., 20222022Аляутдин Р.Н., Романов Б.К.Alyautdin R.N., Romanov B.K.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.risksafety.ru/jour/article/view/314

В обзоре представлены сведения о лекарственных препаратах, обладающих свойствами инверсированных агонистов. Рассмотрены особенности взаимодействия лиганд – рецептор при конститутивной конформационной активности последнего. Многие лиганды, считающиеся нейтральными антагонистами, проявляют в экспериментальных системахотрицательную внутреннюю активность. Это позволяет предположить, что их терапевтическое действие обусловлено не только блокадой рецепторов, но также снижением их спонтанной активности. В статье приведены примеры инверсированных агонистов, влияющих на процессы возбуждения адренергических, гистаминовых, опиоидных, бензодиазепиновых и других рецепторов. Обсуждается взаимосвязь между конститутивной активностью и патофизиологией заболеваний

This review presents information on pharmaceuticals that have the properties of inverse agonists. The article describes the features of the interaction of the ligand - receptor with constitutive conformational changes. Many of ligands, assumed to be neutral antagonists, behave as inverse agonists displaying negative efficacy in experimental systems. This suggests that their therapeutic actions may involve not only receptor blockade, but also the decrease of spontaneous receptor activity. Examples of inverse agonists that influence the processes of excitation of adrenergic, histaminergic, opioid and benzodiazepine receptors are presented. The existence of constitutive activity in vivo and its pathophysiological relevance are also discussed

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