HPTP

HPTP
Clinical data
Drug classSerotonergic and dopaminergic neurotoxin
Identifiers
  • 4-[4-(4-chlorophenyl)-3,6-dihydro-2H-pyridin-1-yl]-1-(4-fluorophenyl)butan-1-one
CAS Number
PubChem CID
ChemSpider
ChEBI
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC21H21ClFNO
Molar mass357.85 g·mol−1
3D model (JSmol)
  • C1CN(CC=C1C2=CC=C(C=C2)Cl)CCCC(=O)C3=CC=C(C=C3)F
  • InChI=1S/C21H21ClFNO/c22-19-7-3-16(4-8-19)17-11-14-24(15-12-17)13-1-2-21(25)18-5-9-20(23)10-6-18/h3-11H,1-2,12-15H2
  • Key:ZNOLNAPJKOYTHY-UHFFFAOYSA-N

HPTP is a monoaminergic neurotoxin related to MPTP. It is the dehydration product of haloperidol. The agent is specifically a dopaminergic and serotonergic neurotoxin. HPTP is a prodrug of HPP+, which mediates its monoaminergic neurotoxicity. This is analogous to how MPP+ mediates the neurotoxicity of MPTP. Other related compounds include RHPTP and RHPP+.

References

  1. 1 2 3 4 5 Kostrzewa RM (2022). "Survey of Selective Monoaminergic Neurotoxins Targeting Dopaminergic, Noradrenergic, and Serotoninergic Neurons". Handbook of Neurotoxicity. Cham: Springer International Publishing. pp. 159–198. doi:10.1007/978-3-031-15080-7_53. ISBN 978-3-031-15079-1.
  2. 1 2 3 4 Igarashi, Kazuo (1998). "The Possible Role of an Active Metabolite Derived from the Neuroleptic Agent Haloperidol in Drug-Induced Parkinsonism". Journal of Toxicology: Toxin Reviews. 17 (1): 27–38. doi:10.3109/15569549809006488. ISSN 0731-3837.
  3. ↑ Górska A, Marszałł M, Sloderbach A (October 2015). "[The neurotoxicity of pyridinium metabolites of haloperidol]" [The neurotoxicity of pyridinium metabolites of haloperidol]. Postepy Higieny I Medycyny Doswiadczalnej (in Polish). 69: 1169–1175. doi:10.5604/17322693.1175009 (inactive 12 July 2025). PMID 26561842.{{cite journal}}: CS1 maint: DOI inactive as of July 2025 (link)
  4. 1 2 3 4 Castagnoli N, Castagnoli KP, Van der Schyf CJ, Usuki E, Igarashi K, Steyn SJ, Riker RR (1999). "Enzyme-catalyzed bioactivation of cyclic tertiary amines to form potential neurotoxins". Pol J Pharmacol. 51 (1): 31–38. PMID 10389142.
  5. ↑ Avent KM, DeVoss JJ, Gillam EM (July 2006). "Cytochrome P450-mediated metabolism of haloperidol and reduced haloperidol to pyridinium metabolites". Chem Res Toxicol. 19 (7): 914–920. doi:10.1021/tx0600090. PMID 16841959.