ArticleBritish journal of pharmacology2019
Intranasal administration of a stapled relaxin-3 mimetic has anxiolytic- and antidepressant-like activity in rats.
Article in British journal of pharmacology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 21 citations in OpenAlex.
- Relaxin family peptide receptor 3 (RXFP3) expressing cells in the zona incerta/lateral hypothalamus augment behavioural arousal.Journal of neurochemistry · 2025Article
- Novel RXFP3 negative allosteric modulator RLX-33 reduces alcohol self-administration in rats.Journal of neurochemistry · 2023Article
- Anxiety and Depression: What Do We Know of Neuropeptides?Behavioral sciences (Basel, Switzerland) · 2022Review
- Advances and Challenges in Intranasal Delivery of Antipsychotic Agents Targeting the Central Nervous System.Frontiers in pharmacology · 2022Review
- Indole-Containing Amidinohydrazones as Nonpeptide, Dual RXFP3/4 Agonists: Synthesis, Structure-Activity Relationship, and Molecular Modeling Studies.Journal of medicinal chemistry · 2021Article
- Exploring the Use of Helicogenic Amino Acids for Optimising Single Chain Relaxin-3 Peptide Agonists.Biomedicines · 2020Article
- Miniproteins as a Powerful Modality in Drug Development.Trends in biochemical sciences · 2020Review
- Development of Relaxin-3 Agonists and Antagonists Based on Grafted Disulfide-Stabilized Scaffolds.Frontiers in chemistry · 2020Article
- Intranasal administration of a stapled relaxin-3 mimetic has anxiolytic- and antidepressant-like activity in rats.British journal of pharmacology · 2019Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
background and purposeDepression and anxiety are common causes of disability, and innovative tools and potential pharmacological targets are actively sought for prevention and treatment. Therapeutic strategies targeting the relaxin-3 peptide or its primary endogenous receptor, RXFP3, for the treatment of major depression and anxiety disorders have been limited by a lack of compounds with drug-like properties. We proposed that a hydrocarbon-stapled mimetic of relaxin-3, when administered intranasally, might be uniquely applicable to the treatment of these disorders. EXPERIMENTAL APPROACH: We designed a series of hydrocarbon-stapled relaxin-3 mimetics and identified the most potent compound using in vitro receptor binding and activation assays. Further, we assessed the effect of intranasal delivery of relaxin-3 and the lead stapled mimetic in rat models of anxiety and depression. KEY
resultsWe developed an i,i+7 stapled relaxin-3 mimetic that manifested a stabilized α-helical structure, proteolytic resistance, and confirmed agonist activity in receptor binding and activation in vitro assays. The stapled peptide agonist enhanced food intake after intracerebral infusion in rats, confirming in vivo activity. We showed that intranasal delivery of the lead i,i+7 stapled peptide or relaxin-3 had orexigenic effects in rats, indicating a potential clinically translatable route of delivery. Further, intranasal administration of the lead i,i+7 stapled peptide exerted anxiolytic and antidepressant-like activity in anxiety- and depression-related behaviour paradigms. CONCLUSIONS AND IMPLICATIONS: Our preclinical findings demonstrate that targeting the relaxin-3/RXFP3 receptor system via intranasal delivery of an i,i+7 stapled relaxin-3 mimetic may represent an effective treatment approach for depression, anxiety, and related neuropsychiatric disorders.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.