Eltoprazine was first described in thescientific literature by 1987.[12][13] It was originated bySolvay and was developed by Elto Pharma, PsychoGenics, and Solvay.[1][5] The drug is or was under development for the treatment of aggression, ADHD, cognitive disorders, and drug-induced dyskinesia, but no recent development has been reported for these indications as of 2022.[1][2] It was also under development for the treatment ofpsychotic disorders, but development for this indication was discontinued.[1][2] Eltoprazine reachedphase 2 or3clinical trials.[1][5][2] According toDavid Nutt, eltoprazine showed shown signs of effectiveness in the treatment of aggression but was rejected for marketing authorization on the basis of aggression being a symptom rather than a disorder.[14][15]
^abcdede Vries MH, de Koning P, Floot HL, Grahnén A, Eckernäs SA, Raghoebar M, et al. (1991). "Dose-proportionality of eltoprazine. Pharmacokinetics of single oral doses in healthy subjects".European Journal of Clinical Pharmacology.41 (5):485–488.doi:10.1007/BF00626375.PMID1761079.
^abcvan Harten J, Mathlener IS, Raghoebar M (1990). "Pharmacokinetics of eltoprazine in healthy subjects".Drug Metabolism and Drug Interactions.8 (1–2):149–158.doi:10.1515/dmdi.1990.8.1-2.149.PMID2091888.
^abcde Boer SF, Koolhaas JM (December 2005). "5-HT1A and 5-HT1B receptor agonists and aggression: a pharmacological challenge of the serotonin deficiency hypothesis".European Journal of Pharmacology.526 (1–3):125–139.doi:10.1016/j.ejphar.2005.09.065.PMID16310183.
^Olivier B, van Oorschot R (December 2005). "5-HT1B receptors and aggression: a review".European Journal of Pharmacology.526 (1–3):207–217.doi:10.1016/j.ejphar.2005.09.066.PMID16310769.
^De Almeida Santos G, Schwaneberg U, Blank LM (2020).Engineering of heme-dependent monooxygenases towards heterocycle conversion (Thesis). RWTH Aachen University.doi:10.18154/rwth-2020-10487. Retrieved19 January 2026.Additionally, the benzo-1,4-dioxane ring is present in drug precursors such as eltoprazine [150,151] which is itself a precursor for S-15535 and Lecozotan (Phase III trials completed in 2008 [152]).
^Olivier B, Mos J, Heyden VD, Zethof T, Aken VH, Oorschot VR, et al. (1987). "Effects of DU 28853, a new serenic drug, in several experimental models for aggression".Research on Aggression.93.
^Schipper J, Olivier B, Mos J, Tulp MT, Sijbesma H, Bevan P (1987).Eltoprazine (DU 28853): Effects on aggressive behaviour and its serotonergic properties. International Conference on the Behavioral Pharmacology.
^Nutt DJ (March 2025). "Drug development in psychiatry: 50 years of failure and how to resuscitate it".The Lancet. Psychiatry.12 (3):228–238.doi:10.1016/S2215-0366(24)00370-5.PMID39952266.Marketing authorisations are awarded for diagnoses, whereas in clinical practice psychiatrists and primary care physicians commonly treat symptoms, such as insomnia, which occurs in many different disorders as well as being a disorder itself.72 A good example of the discrepancy that thus arises was the development of the serotonin agonist eltoprazine, which proved effective for aggression in people with learning disabilities.53 EMA marketing authorisation was denied on the grounds that aggression was a symptom, not a diagnosis. Perversely, 18 years later, the dopamine–serotonin antagonist antipsychotic risperidone was approved for the same indication.73 [...] 53 de Koning P, Mak M, de Vries MH, et al. Eltoprazine in aggressive mentally handicapped patients: a double-blind, placebo- and baseline-controlled multi-centre study. Int Clin Psychopharmacol 1994; 9: 187–94.
^de Koning P, Mak M, de Vries MH, Allsopp LF, Stevens RB, Verbruggen R, et al. (September 1994). "Eltoprazine in aggressive mentally handicapped patients: a double-blind, placebo- and baseline-controlled multi-centre study. The Eltoprazine Aggression Research Group".International Clinical Psychopharmacology.9 (3):187–194.doi:10.1097/00004850-199409000-00007.PMID7814828.
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