Chemistry:Eltoprazine

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Eltoprazine (INN; developmental code name DU-28,853) is a non-selective serotonin receptor modulator of the phenylpiperazine family which was under development for the treatment of aggression, attention deficit hyperactivity disorder (ADHD), cognition disorders, drug-induced dyskinesia, and psychotic disorders but was never marketed.[1][2][3][4][5] It has been described as a "serenic" or antiaggressive agent.[4][5] The drug is taken orally.[1][3]

It acts as an agonist of the serotonin 5-HT1A and 5-HT1B receptors and as an antagonist of the serotonin 5-HT2C receptor (Ki = 40 nM, 52 nM, and 81 nM, respectively).[5][6] The drug also shows weaker affinity for certain other serotonin receptors and targets.[6] The pharmacokinetics of eltoprazine have been studied.[7][8] Eltoprazine is closely related to fluprazine and batoprazine, which are similarly acting agents,[9][10] and is also a known chemical precursor to S-15535 and lecozotan.[11]

Eltoprazine was first described in the scientific literature by 1987.[12][13] It was originated by Solvay and was developed by Elto Pharma, PsychoGenics, and Solvay.[1][2] 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][3] It was also under development for the treatment of psychotic disorders, but development for this indication was discontinued.[1][3] Eltoprazine reached phase 2 or 3 clinical trials.[1][2][3] According to David 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]

See also

  • Substituted phenylpiperazine
  • List of investigational aggression drugs

References

  1. ↑ 1.0 1.1 1.2 1.3 1.4 1.5 "Eltoprazine - Elto Pharma". AdisInsight. https://adisinsight.springer.com/drugs/800000719. 
  2. ↑ 2.0 2.1 2.2 "Delving into the Latest Updates on Eltoprazine Hydrochloride with Synapse". 18 June 2025. https://synapse.patsnap.com/drug/540d07e755af44c4b3eff4bb44a37cc2. 
  3. ↑ 3.0 3.1 3.2 3.3 3.4 "Eltoprazine Drug Profile". 1 January 1900. https://pryzm.ozmosi.com/product/725. 
  4. ↑ 4.0 4.1 "Behavioural pharmacology of the serenic, eltoprazine". Drug Metabolism and Drug Interactions 8 (1–2): 31–83. 1990. doi:10.1515/DMDI.1990.8.1-2.31. PMID 2091890. 
  5. ↑ 5.0 5.1 5.2 "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. December 2005. doi:10.1016/j.ejphar.2005.09.065. PMID 16310183. 
  6. ↑ 6.0 6.1 "Neurochemical profile of eltoprazine". Drug Metabolism and Drug Interactions 8 (1–2): 85–114. 1990. doi:10.1515/dmdi.1990.8.1-2.85. PMID 1982626. 
  7. ↑ "Dose-proportionality of eltoprazine. Pharmacokinetics of single oral doses in healthy subjects". European Journal of Clinical Pharmacology 41 (5): 485–488. 1991. doi:10.1007/BF00626375. PMID 1761079. 
  8. ↑ "Pharmacokinetics of eltoprazine in healthy subjects". Drug Metabolism and Drug Interactions 8 (1–2): 149–158. 1990. doi:10.1515/dmdi.1990.8.1-2.149. PMID 2091888. 
  9. ↑ "5-HT1B receptors and aggression: a review". European Journal of Pharmacology 526 (1–3): 207–217. December 2005. doi:10.1016/j.ejphar.2005.09.066. PMID 16310769. 
  10. ↑ "Serotonergic mechanisms in aggression". Novartis Foundation Symposia. 268. Wiley. 28 July 2005. pp. 171–189. doi:10.1002/0470010703.ch12. ISBN 978-0-470-01068-6. https://onlinelibrary.wiley.com/doi/10.1002/0470010703.ch12. Retrieved 19 January 2026. 
  11. ↑ 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. Retrieved 19 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]).
  12. ↑ "Effects of DU 28853, a new serenic drug, in several experimental models for aggression.". Research on Aggression 93. 1987. 
  13. ↑ "Eltoprazine (DU 28853): Effects on aggressive behaviour and its serotonergic properties.". International Conference on the Behavioral Pharmacology. 1987. 
  14. ↑ "Drug development in psychiatry: 50 years of failure and how to resuscitate it". The Lancet. Psychiatry 12 (3): 228–238. March 2025. doi:10.1016/S2215-0366(24)00370-5. PMID 39952266. "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.". 
  15. ↑ "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. September 1994. doi:10.1097/00004850-199409000-00007. PMID 7814828. 



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