ArticleJournal of neurochemistry2023
Novel RXFP3 negative allosteric modulator RLX-33 reduces alcohol self-administration in rats.
Article in Journal of neurochemistry, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
4 citing papers in PubMed, 9 citations in OpenAlex.
- Prelimbic cortex, but not its nucleus reuniens projections, regulates punished alcohol self-administration.Neuropharmacology · 2026Article
- Individual differences in punished alcohol self-administration are unaltered by alcohol vapor exposure.Alcohol (Fayetteville, N.Y.) · 2025Observational
- Development of Diphenyl-1,2,4-Oxadiazole Analogues as Allosteric Modulators of the RXFP3 Receptor: Evaluation of Importance of the N-Substituted-2-Pyrrolidone Moiety in RLX-33.Journal of medicinal chemistry · 2025Article
- Targeting the relaxin-3/RXFP3 system: a patent review for the last two decades.Expert opinion on therapeutic patentsReview
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
There is much interest in identifying novel pharmacotherapeutic targets that improve clinical outcomes for the treatment of alcohol use disorder (AUD). One promising target for therapeutic intervention is the relaxin family peptide 3 (RXFP3) receptor, a cognate receptor for neuropeptide relaxin-3, which has previously been implicated in regulating alcohol drinking behavior. Recently, we developed the first small-molecule RXFP3-selective negative allosteric modulator (NAM) RLX-33. Therefore, the goal of the present work was to characterize the impact of this novel NAM on affective-related behaviors and alcohol self-administration in rats. First, the effects of RLX-33 were tested on alcohol and sucrose self-administration in Wistar and alcohol-preferring P rats to determine the dose-response profile and specificity for alcohol. Then, we assessed the effects of systemic RLX-33 injection in Wistar rats in a battery of behavioral assays (open-field test, elevated zero maze, acoustic startle response test, and prepulse inhibition) and tested for alcohol clearance. We found that the lowest effective dose (5 mg/kg) reduced alcohol self-administration in both male and female Wistar rats, while in alcohol-preferring P rats, this effect was restricted to males, and there were no effects on sucrose self-administration or general locomotor activity. The characterization of affective and metabolic effects in Wistar rats generally found few locomotor, affective, or alcohol clearance changes, particularly at the 5 mg/kg dose. Overall, these findings are promising and suggest that RXFP3 NAM has potential as a pharmacological target for treating AUD.
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Registered trials
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.