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AB0124 is a serotonin 5-HT2A receptor positive allosteric modulator.[1][2][3] It is highly selective for potentiation of the serotonin 5-HT2A receptor, with no potentiation of the serotonin 5-HT2B and 5-HT2C receptors.[1][2] In addition, it showed no orthosteric agonistic activity at any of the serotonin 5-HT2 receptors.[1] AB0124 has been studied in combination with the serotonin 5-HT2 receptor agonist (R)-DOI in animal models of cocaine use disorder.[2][1] The chemical synthesis of AB0124 has been described.[3] The drug was patented in 2022[3] and was first described in the scientific literature by 2024.[2][1]

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References

  1. ^ a b c d e Merritt RF, Anastasio N, Zhou J, Cunningham K (January 2026). “ACNP 64th Annual Meeting: Poster Abstracts P292-583”. Neuropsychopharmacology. 51 (Suppl 1): 243–409. doi:10.1038/s41386-025-02280-3. PMC 12783661. PMID 41507445.
  2. ^ a b c d Bolinger AA, Zamora J, Merritt CR, Anastasio NC, Cunningham KA, Zhou J (March 2024). Discovery of novel serotonin 5-HT2A receptor positive allosteric modulators (PDF). 16TH Annual Behavior, Biology, and Chemistry: Translational Research in Substance Use Disorders, San Antonio, Texas | Embassy Landmark | 22-24 March 2024. Synthesizing and screening novel small molecules, we identified potent positive allosteric modulators (PAMs) of 5-HT2AR. Further analysis and comparison against CNS receptors, channels, and transporters led to the identification of AB0124 a potential candidate with high specificity. This compound has demonstrated functional increases in 5-HT-induced Ca2+ release at the micromolar level for the 5-HT2AR over other serotonin receptors. With promising in vitro pharmacological and physicochemical profiles, our novel 5-HT2AR PAMs hold potential as neurotherapeutics for [cocaine use disorder (CUD)].
  3. ^ a b c WO 2023/023287A1, Zhou J, Cunningham KA, Bolinger AA, Anastasio NC, ”Novel heterocyclic compounds as serotonin (5-ht) 5-ht2a and 5-ht2c receptor positive allosteric modulators”, issued 23 February 2023, assigned to University of Texas System, University of Texas at Austin