Eltoprazine

Last updated
Eltoprazine
Eltoprazine.svg
Clinical data
Other namesDU-28,853; DU-28853; DU28853
Routes of
administration 		Oral [1] [2]
Drug class Non-selective serotonin receptor modulator; Serotonin 5-HT1A receptor agonist; Serotonin 5-HT1B receptor agonist; Serotonin 5-HT2C receptor
ATC code
  • None
Pharmacokinetic data
Bioavailability 95% [3] [4]
Onset of action 1–4 hours (Tmax Tooltip time to peak) [3]
Elimination half-life 7–9 hours [3] [4]
Excretion Urine: 40% unchanged [3]
Identifiers
  • 1-(2,3-dihydro-1,4-benzodioxin-5-yl)piperazine
CAS Number
PubChem CID
ChemSpider
UNII
ChEBI
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
Formula C12H16N2O2
Molar mass 220.272 g·mol−1
3D model (JSmol)
  • C1CN(CCN1)C2=C3C(=CC=C2)OCCO3
  • InChI=1S/C12H16N2O2/c1-2-10(14-6-4-13-5-7-14)12-11(3-1)15-8-9-16-12/h1-3,13H,4-9H2
  • Key:WVLHGCRWEHCIOT-UHFFFAOYSA-N

Eltoprazine (INN Tooltip International Nonproprietary Name; 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] [5] [2] [6] [7] It has been described as a "serenic" or antiaggressive agent. [6] [7] The drug is taken orally. [1] [2]

Contents

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). [7] [8] The drug also shows weaker affinity for certain other serotonin receptors and targets. [8] The pharmacokinetics of eltoprazine have been studied. [3] [4] 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] [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 of psychotic disorders, but development for this indication was discontinued. [1] [2] Eltoprazine reached phase 2 or 3 clinical trials. [1] [5] [2] 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

References

  1. 1 2 3 4 5 6 7 "Eltoprazine - Elto Pharma - AdisInsight".
  2. 1 2 3 4 5 6 "Eltoprazine Drug Profile". Ozmosi. 1 January 1900. Retrieved 19 January 2026.
  3. 1 2 3 4 5 de Vries MH, de Koning P, Floot HL, Grahnén A, Eckernäs SA, Raghoebar M, Dahlström B, Ekman L (1991). "Dose-proportionality of eltoprazine. Pharmacokinetics of single oral doses in healthy subjects". Eur J Clin Pharmacol. 41 (5): 485–488. doi:10.1007/BF00626375. PMID   1761079.
  4. 1 2 3 van Harten J, Mathlener IS, Raghoebar M (1990). "Pharmacokinetics of eltoprazine in healthy subjects". Drug Metabol Drug Interact. 8 (1–2): 149–158. doi:10.1515/dmdi.1990.8.1-2.149. PMID   2091888.
  5. 1 2 3 "Delving into the Latest Updates on Eltoprazine Hydrochloride with Synapse". Synapse. 18 June 2025. Retrieved 19 January 2026.
  6. 1 2 Olivier B, Mos J, Rasmussen D (1990). "Behavioural pharmacology of the serenic, eltoprazine". Drug Metabol Drug Interact. 8 (1–2): 31–83. doi:10.1515/DMDI.1990.8.1-2.31. PMID   2091890. S2CID   27279453.
  7. 1 2 3 de Boer SF, Koolhaas JM (December 2005). "5-HT1A and 5-HT1B receptor agonists and aggression: a pharmacological challenge of the serotonin deficiency hypothesis". Eur J Pharmacol. 526 (1–3): 125–39. doi:10.1016/j.ejphar.2005.09.065. PMID   16310183.
  8. 1 2 Schipper J, Tulp MT, Sijbesma H (1990). "Neurochemical profile of eltoprazine". Drug Metabol Drug Interact. 8 (1–2): 85–114. doi:10.1515/dmdi.1990.8.1-2.85. PMID   1982626. S2CID   30096596.
  9. ↑ Olivier B, van Oorschot R (December 2005). "5-HT1B receptors and aggression: a review". Eur J Pharmacol. 526 (1–3): 207–217. doi:10.1016/j.ejphar.2005.09.066. PMID   16310769.
  10. ↑ Olivier, Berend (28 July 2005). "Serotonergic mechanisms in aggression". Novartis Foundation Symposia. Vol. 268. Wiley. p. 171–189. doi:10.1002/0470010703.ch12. ISBN   978-0-470-01068-6 . Retrieved 19 January 2026.
  11. ↑ De Almeida Santos, Gustavo; Schwaneberg, Ulrich; Blank, Lars M. (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. ↑ Olivier, B., Mos, J., Heyden, V. D. J. A., Zethof, T., Aken, V. H., Oorschot, V. R., & Ramirez, J. M. (1987). Effects of DU 28853, a new serenic drug, in several experimental models for aggression. Research on Aggression, 93. https://scholar.google.com/scholar?cluster=5474933454486255245
  13. ↑ Schipper, J., Olivier, B., Mos, J., Tulp, M. T. M., Sijbesma, H., & Bevan, P. (1987). Eltoprazine (DU 28853): Effects on aggressive behaviour and its serotonergic properties. In International Conference on the Behavioral Pharmacology of [...]. https://scholar.google.com/scholar?cluster=17685819389699199278
  14. ↑ Nutt DJ (March 2025). "Drug development in psychiatry: 50 years of failure and how to resuscitate it". Lancet Psychiatry. 12 (3): 228–238. 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. ↑ de Koning P, Mak M, de Vries MH, Allsopp LF, Stevens RB, Verbruggen R, Van den Borre R, van Peteghem P, Kohen D, Arumainayagam M (September 1994). "Eltoprazine in aggressive mentally handicapped patients: a double-blind, placebo- and baseline-controlled multi-centre study. The Eltoprazine Aggression Research Group". Int Clin Psychopharmacol. 9 (3): 187–194. PMID   7814828.
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