NLX-204 is a drug that as of 2026 is being evaluated to treat depression. It is a selective biased agonist of the serotonin 5-HT1A receptor, distinguished by its preference for activating ERK1/ERK2 phosphorylation pathways.[1][2]

This compound has demonstrated potent and rapid-acting antidepressant-like effects in preclinical models, with activity comparable to ketamine in reversing symptoms of depression and treatment-resistant depression in rodents. Recent studies suggest that NLX-204 also offers potential benefits reversing memory deficits and anxiety, positioning it as a candidate for a rapid-acting antidepressant therapy.[3][4]

Chemistry

Synthesis

NLX-204 is synthesized from 3-chloro-4-fluorobenzoic acid. Conversion to the corresponding benzoyl chloride followed by amidation with 4-piperidone yields a benzoylpiperidone intermediate. A Darzens reaction with chloroacetonitrile produces a cyanoepoxide, which undergoes regioselective ring opening with poly(hydrogen fluoride)pyridine to form a cyanohydrin. Final reductive amination with 2-(pyridin-2-yloxy)ethanamine in the presence of sodium cyanoborohydride affords NLX-204.[1]

See also

References

  1. 1 2
  2. ↑ Papp M, Gruca P, Lason M, Litwa E, Newman-Tancredi A, Depoortère R (November 2023). "The 5-HT1A receptor biased agonists, NLX-204 and NLX-101, display ketamine-like RAAD and anti-TRD activities in rat CMS models". Psychopharmacology. 240 (11): 2419–2433. doi:10.1007/s00213-023-06389-5. PMC 10593613. PMID 37310446.
  3. ↑ Głuch-Lutwin M, Sałaciak K, Pytka K, Gawalska A, Jamrozik M, Śniecikowska J, et al. (February 2023). "The 5-HT1A receptor biased agonist, NLX-204, shows rapid-acting antidepressant-like properties and neurochemical changes in two mouse models of depression". Behavioural Brain Research. 438 114207. doi:10.1016/j.bbr.2022.114207. PMID 36368443.
allikas: https://en.wikipedia.org/wiki/NLX-204