Barettin, a Nonopioid, Nonhallucinogenic Marine Natural Product with Antihyperalgesic Properties Mediated by 5HT2A Inverse Agonism

Journal of Natural Products 2026 Open access

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Authors: Caleb A. Seekins, Michael Okine, Emily G. Forrest, Timothy Chavez, Alexandra Stump, Vishal Kaleeswaran, Jerry E. Carr, Christopher Hulme, Paco Cárdenas, Todd W. Vanderah, John M. Streicher, Christopher Cartmell
DOI: 10.1021/acs.jnatprod.6c00169
Cited by: 1
References: 55

Abstract

Despite increasing interest, there remain limited treatments for chronic pain, with opioids continuing to be one of the top prescribed medications. Marine natural products present a wealth of untapped potential for new treatments for chronic pain. In this study, we investigated the analgesic effects of the sea sponge ligand barettin in a mouse model of chemotherapy-induced peripheral neuropathy (CIPN). Barettin exhibited efficacious antihyperalgesic activity in male mice with no efficacy shown in females. Through the use of a PRESTO-Tango assay, we found that barettin acts as an inverse agonist at the 5HT2A receptor while also presenting no activity at the μ-opioid receptor. Head twitch experiments confirmed no hallucinogenic activity, suggesting that barettin may be a promising nonopioid, nonhallucinogenic, marine-derived therapeutic agent for the treatment of chronic pain.

Fields of Study & Subjects

Marine Sponges and Natural Products Seaweed-derived Bioactive Compounds Marine Toxins and Detection Methods

Publication details

Journal / source
Journal of Natural Products
Publisher
American Chemical Society (ACS)
Volume
89
Issue
4
Pages
1298–1308
Publication date
31 March 2026
Language
EN