Fluperlapine

Summary

Fluperlapine (NB 106-689), also known as fluoroperlapine, is a morphanthridine (11H-dibenzo[b,e]azepine) atypical antipsychotic with additional antidepressant and sedative effects. It was first synthesized in 1979, and then subsequently studied in animals and humans in 1984 and beyond,[1] but despite demonstrating efficacy in the treatment of a variety of medical conditions including schizophrenia,[2][3][4][5] psychosis associated with Parkinson's disease,[6] depressive symptoms, and dystonia,[7] it was never marketed.[1] This was perhaps due to its capacity for producing potentially life-threatening agranulocytosis, similarly to clozapine,[8] which it closely resembles both structurally and pharmacologically.

Fluperlapine
Clinical data
ATC code
  • none
Identifiers
  • 3-fluoro-6-(4-methylpiperazin-1-yl)-11H-dibenzo[b,e]azepine
CAS Number
  • 67121-76-0 ☒N
PubChem CID
  • 49381
ChemSpider
  • 44882 checkY
UNII
  • EWG253M961
ChEMBL
  • ChEMBL63756 checkY
CompTox Dashboard (EPA)
  • DTXSID2046123 Edit this at Wikidata
Chemical and physical data
FormulaC19H20FN3
Molar mass309.388 g·mol−1
3D model (JSmol)
  • Interactive image
  • Fc4ccc3c(/N=C(/N1CCN(C)CC1)c2ccccc2C3)c4
  • InChI=1S/C19H20FN3/c1-22-8-10-23(11-9-22)19-17-5-3-2-4-14(17)12-15-6-7-16(20)13-18(15)21-19/h2-7,13H,8-12H2,1H3 checkY
  • Key:OBWGMKKHCLHVIE-UHFFFAOYSA-N checkY
 ☒NcheckY (what is this?)  (verify)

Pharmacology edit

Binding profile[9]

Receptor Ki (nM)
5-HT2A 7.9
5-HT2C 18.2
5-HT6 29
5-HT7 4.6
M1 8.8
M2 71
M3 41
M4 14
M5 17
D1 85
D2 316.2
D3 254.7
D4 21

Synthesis edit

 
Patents:[10][11]

3-fluoro-5,11-dihydro-6H-dibenz[b,e]azepin-6-one [62662-88-8] (3)

See also edit

References edit

  1. ^ a b Ganellin CR, Triggle DJ, Macdonald F (1997). Dictionary of pharmacological agents. CRC Press. p. 916. ISBN 978-0-412-46630-4. Retrieved 15 September 2011.
  2. ^ Fischer-Cornelssen KA (1984). "Fluperlapine in 104 schizophrenic patients. Open multicenter trial". Arzneimittel-Forschung. 34 (1A): 125–30. PMID 6145428.
  3. ^ Woggon B, Angst J, Bartels M, Heinrich K, Hippius H, Koukkou M, et al. (1984). "Antipsychotic efficacy of fluperlapine. An open multicenter trial". Neuropsychobiology. 11 (2): 116–20. doi:10.1159/000118064. PMID 6148712.
  4. ^ Dieterle D, Eben E, Einhäupl K, Hippius H, Klein H, Rüther E, Schmauss M (March 1984). "The effect of fluperlapine in acute psychotic patients". Pharmacopsychiatry. 17 (2): 57–60. doi:10.1055/s-2007-1017408. PMID 6728910. S2CID 22264476.
  5. ^ Woggon B, Heinrich K, Küfferle B, Müller-Oerlinghausen B, Pöldinger W, Rüther E, Schied HW (1984). "Results of a multicenter AMDP study with fluperlapine in schizophrenic patients". Arzneimittel-Forschung. 34 (1A): 122–4. PMID 6145427.
  6. ^ Scholz E, Dichgans J (1985). "Treatment of drug-induced exogenous psychosis in parkinsonism with clozapine and fluperlapine". European Archives of Psychiatry and Neurological Sciences. 235 (1): 60–4. doi:10.1007/bf00380972. PMID 2864254. S2CID 23735955.
  7. ^ Pakkenberg H, Pedersen B (1985). "Medical treatment of dystonia". Dyskinesia. Psychopharmacology Supplementum. Vol. 2. pp. 111–7. doi:10.1007/978-3-642-70140-5_14. ISBN 978-3-642-70142-9. OCLC 10642795. PMID 2860654.
  8. ^ Lai WG, Gardner I, Zahid N, Uetrecht JP (March 2000). "Bioactivation and covalent binding of hydroxyfluperlapine in human neutrophils: implications for fluperlapine-induced agranulocytosis". Drug Metabolism and Disposition. 28 (3): 255–63. PMID 10681368.
  9. ^ Roth BL, Driscol J (12 January 2011). "PDSP Ki Database". Psychoactive Drug Screening Program (PDSP). University of North Carolina at Chapel Hill and the United States National Institute of Mental Health. Archived from the original on 8 November 2013. Retrieved 3 December 2013.
  10. ^ Fritz Hunziker, Rudolf Fischer, U.S. patent 4,308,207 (1981 to Sandoz Ltd.).
  11. ^ Fritz Hunziker & Rudolf Fischer, U.S. patent 4,406,900 (1983 to Fidelity Union Bank).