Fluperlapine

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.

ATC code

none

CAS Number

67121-76-0^N

PubChem CID

49381

ChemSpider

44882^Y

Quick facts Clinical data, ATC code ...

Fluperlapine
Clinical data

ATC code	none
Identifiers
IUPAC name 3-fluoro-6-(4-methylpiperazin-1-yl)-11H-dibenzo[b,e]azepine
CAS Number	67121-76-0^N
PubChem CID	49381
ChemSpider	44882^Y
UNII	EWG253M961
ChEMBL	ChEMBL63756^Y
CompTox Dashboard (EPA)	DTXSID2046123
Chemical and physical data
Formula	C₁₉H₂₀FN₃
Molar mass	309.388 g·mol⁻¹
3D model (JSmol)	Interactive image
SMILES Fc4ccc3c(/N=C(/N1CCN(C)CC1)c2ccccc2C3)c4
InChI 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^Y Key:OBWGMKKHCLHVIE-UHFFFAOYSA-N^Y
^NY (what is this?) (verify)

Pharmacology

Binding profile^[9]

More information Receptor, Ki (nM) ...

Receptor	K_i (nM)
5-HT_2A	7.9
5-HT_2C	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

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

References

[1]
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 K_i 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).

Pharmacology

Synthesis

See also

References

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