Fluperlapine Explained

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.

Pharmacology

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

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

See also

• Clozapine
• Perlapine

Notes and References

1. Book: Ganellin CR, Triggle DJ, Macdonald F . Dictionary of pharmacological agents . 15 September 2011 . 1997 . . 978-0-412-46630-4 . 916 .
2. Fischer-Cornelssen KA . Fluperlapine in 104 schizophrenic patients. Open multicenter trial . Arzneimittel-Forschung . 34 . 1A . 125–30 . 1984 . 6145428 .
3. Woggon B, Angst J, Bartels M, Heinrich K, Hippius H, Koukkou M, Krebs E, Küfferle B, Müller-Oerlinghausen B, Pöldinger W . 6 . Antipsychotic efficacy of fluperlapine. An open multicenter trial . Neuropsychobiology . 11 . 2 . 116–20 . 1984 . 6148712 . 10.1159/000118064 .
4. Dieterle D, Eben E, Einhäupl K, Hippius H, Klein H, Rüther E, Schmauss M . The effect of fluperlapine in acute psychotic patients . Pharmacopsychiatry . 17 . 2 . 57–60 . March 1984 . 6728910 . 10.1055/s-2007-1017408 . 22264476 .
5. Woggon B, Heinrich K, Küfferle B, Müller-Oerlinghausen B, Pöldinger W, Rüther E, Schied HW . Results of a multicenter AMDP study with fluperlapine in schizophrenic patients . Arzneimittel-Forschung . 34 . 1A . 122–4 . 1984 . 6145427 .
6. Scholz E, Dichgans J . Treatment of drug-induced exogenous psychosis in parkinsonism with clozapine and fluperlapine . European Archives of Psychiatry and Neurological Sciences . 235 . 1 . 60–4 . 1985 . 2864254 . 10.1007/bf00380972 . 23735955 .
7. Book: Pakkenberg H, Pedersen B . Dyskinesia . Medical treatment of dystonia . 2 . 111–7 . 1985 . 2860654 . 10.1007/978-3-642-70140-5_14 . 978-3-642-70142-9 . Psychopharmacology Supplementum . 10642795 .
8. Lai WG, Gardner I, Zahid N, Uetrecht JP . Bioactivation and covalent binding of hydroxyfluperlapine in human neutrophils: implications for fluperlapine-induced agranulocytosis . Drug Metabolism and Disposition . 28 . 3 . 255–63 . March 2000 . 10681368 .
9. Web site: PDSP K_i Database . Psychoactive Drug Screening Program (PDSP). Bryan Roth . Roth BL, Driscol J . University of North Carolina at Chapel Hill and the United States National Institute of Mental Health . 3 December 2013 . 12 January 2011 . dead . https://web.archive.org/web/20131108013656/http://pdsp.med.unc.edu/pdsp.php . 8 November 2013 .