Fluperlapine

Last updated

Fluperlapine
Fluperlapine.svg
Clinical data
ATC code
  • none
Identifiers
  • 3-fluoro-6-(4-methylpiperazin-1-yl)-11H-dibenzo[b,e]azepine
CAS Number
PubChem CID
ChemSpider
UNII
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
Formula C19H20FN3
Molar mass 309.388 g·mol−1
3D model (JSmol)
  • 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 Yes check.svgY
  • Key:OBWGMKKHCLHVIE-UHFFFAOYSA-N Yes check.svgY
 X mark.svgNYes check.svgY  (what is this?)    (verify)

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.

Contents

Pharmacology

Binding profile [9]

ReceptorKi (nM)
5-HT2A7.9
5-HT2C18.2
5-HT629
5-HT74.6
M18.8
M271
M341
M414
M517
D185
D2316.2
D3254.7
D421

Synthesis

Patents: Fluperlapine synthesis.svg
Patents:

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

See also

Related Research Articles

<span class="mw-page-title-main">Antipsychotic</span> Class of medications

Antipsychotics, previously known as neuroleptics and major tranquilizers, are a class of psychotropic medication primarily used to manage psychosis, principally in schizophrenia but also in a range of other psychotic disorders. They are also the mainstay, together with mood stabilizers, in the treatment of bipolar disorder. Moreover, they are also used as adjuncts in the treatment of treatment-resistant major depressive disorder.

<span class="mw-page-title-main">Clozapine</span> Atypical antipsychotic medication

Clozapine is a psychiatric medication and was the first atypical antipsychotic to be discovered. It is primarily used to treat people with schizophrenia and schizoaffective disorder who have had an inadequate response to two other antipsychotics, or who have been unable to tolerate other drugs due to extrapyramidal side effects. It is also used for the treatment of psychosis in Parkinson's disease.

<span class="mw-page-title-main">Fluphenazine</span> Typical antipsychotic medication

Fluphenazine, sold under the brand name Prolixin among others, is a high-potency typical antipsychotic medication. It is used in the treatment of chronic psychoses such as schizophrenia, and appears to be about equal in effectiveness to low-potency antipsychotics like chlorpromazine. It is given by mouth, injection into a muscle, or just under the skin. There is also a long acting injectable version that may last for up to four weeks. Fluphenazine decanoate, the depot injection form of fluphenazine, should not be used by people with severe depression.

<span class="mw-page-title-main">Typical antipsychotic</span> Class of drugs

Typical antipsychotics are a class of antipsychotic drugs first developed in the 1950s and used to treat psychosis. Typical antipsychotics may also be used for the treatment of acute mania, agitation, and other conditions. The first typical antipsychotics to come into medical use were the phenothiazines, namely chlorpromazine which was discovered serendipitously. Another prominent grouping of antipsychotics are the butyrophenones, an example of which is haloperidol. The newer, second-generation antipsychotics, also known as atypical antipsychotics, have largely supplanted the use of typical antipsychotics as first-line agents due to the higher risk of movement disorders with typical antipsychotics.

<span class="mw-page-title-main">Atypical antipsychotic</span> Class of pharmaceutical drugs

The atypical antipsychotics (AAP), also known as second generation antipsychotics (SGAs) and serotonin–dopamine antagonists (SDAs), are a group of antipsychotic drugs largely introduced after the 1970s and used to treat psychiatric conditions. Some atypical antipsychotics have received regulatory approval for schizophrenia, bipolar disorder, irritability in autism, and as an adjunct in major depressive disorder.

<span class="mw-page-title-main">Quetiapine</span> Atypical antipsychotic medication

Quetiapine, sold under the brand name Seroquel among others, is an atypical antipsychotic medication used for the treatment of schizophrenia, bipolar disorder, and major depressive disorder. Despite being widely used as a sleep aid due to its sedating effect, the benefits of such use may not outweigh its undesirable side effects. It is taken orally.

<span class="mw-page-title-main">Olanzapine</span> Atypical antipsychotic medication

Olanzapine, sold under the brand name Zyprexa among others, is an atypical antipsychotic primarily used to treat schizophrenia and bipolar disorder. For schizophrenia, it can be used for both new-onset disease and long-term maintenance. It is taken by mouth or by injection into a muscle.

<span class="mw-page-title-main">Perphenazine</span> Antipsychotic medication

Perphenazine is a typical antipsychotic drug. Chemically, it is classified as a piperazinyl phenothiazine. Originally marketed in the United States as Trilafon, it has been in clinical use for decades.

<span class="mw-page-title-main">Sertindole</span> Antipsychotic medication

Sertindole, sold under the brand name Serdolect among others, is an antipsychotic medication. Sertindole was developed by the Danish pharmaceutical company Lundbeck and marketed under license by Abbott Labs. Like other atypical antipsychotics, it has activity at dopamine and serotonin receptors in the brain. It is used in the treatment of schizophrenia. It is classified chemically as a phenylindole derivative.

<span class="mw-page-title-main">Amoxapine</span> Tricyclic antidepressant medication

Amoxapine, sold under the brand name Asendin among others, is a tricyclic antidepressant (TCA). It is the N-demethylated metabolite of loxapine. Amoxapine first received marketing approval in the United States in 1980, approximately 10 to 20 years after most of the other TCAs were introduced in the United States.

<span class="mw-page-title-main">Dopaminergic</span> Substance related to dopamine functions

Dopaminergic means "related to dopamine" (literally, "working on dopamine"), dopamine being a common neurotransmitter. Dopaminergic substances or actions increase dopamine-related activity in the brain. Dopaminergic brain pathways facilitate dopamine-related activity. For example, certain proteins such as the dopamine transporter (DAT), vesicular monoamine transporter 2 (VMAT2), and dopamine receptors can be classified as dopaminergic, and neurons that synthesize or contain dopamine and synapses with dopamine receptors in them may also be labeled as dopaminergic. Enzymes that regulate the biosynthesis or metabolism of dopamine such as aromatic L-amino acid decarboxylase or DOPA decarboxylase, monoamine oxidase (MAO), and catechol O-methyl transferase (COMT) may be referred to as dopaminergic as well. Also, any endogenous or exogenous chemical substance that acts to affect dopamine receptors or dopamine release through indirect actions (for example, on neurons that synapse onto neurons that release dopamine or express dopamine receptors) can also be said to have dopaminergic effects, two prominent examples being opioids, which enhance dopamine release indirectly in the reward pathways, and some substituted amphetamines, which enhance dopamine release directly by binding to and inhibiting VMAT2.

<span class="mw-page-title-main">Amisulpride</span> Atypical antipsychotic and antiemetic medication

Amisulpride is an antiemetic and antipsychotic medication used at lower doses intravenously to prevent and treat postoperative nausea and vomiting; and at higher doses by mouth to treat schizophrenia and acute psychotic episodes. It is sold under the brand names Barhemsys and Solian, Socian, Deniban and others. At very low doses it is also used to treat dysthymia.

<span class="mw-page-title-main">Sulpiride</span> Atypical antipsychotic

Sulpiride, sold under the brand name Dogmatil among others, is an atypical antipsychotic medication of the benzamide class which is used mainly in the treatment of psychosis associated with schizophrenia and major depressive disorder, and is sometimes used in low dosage to treat anxiety and mild depression. Sulpiride is commonly used in Asia, Central America, Europe, South Africa and South America. Levosulpiride is its purified levo-isomer and is sold in India for similar purposes. It is not approved in the United States, Canada, or Australia. The drug is chemically and clinically similar to amisulpride.

<span class="mw-page-title-main">Flupentixol</span> Typical antipsychotic drug of the thioxanthene class

Flupentixol (INN), also known as flupenthixol, marketed under brand names such as Depixol and Fluanxol is a typical antipsychotic drug of the thioxanthene class. It was introduced in 1965 by Lundbeck. In addition to single drug preparations, it is also available as flupentixol/melitracen—a combination product containing both melitracen and flupentixol . Flupentixol is not approved for use in the United States. It is, however, approved for use in the UK, Australia, Canada, Russian Federation, South Africa, New Zealand, Philippines, Iran, Germany, and various other countries.

<span class="mw-page-title-main">Zotepine</span> Atypical antipsychotic medication

Zotepine is an atypical antipsychotic drug indicated for acute and chronic schizophrenia. It has been used in Germany since 1990 and Japan since 1982.

<span class="mw-page-title-main">Melperone</span> Antipsychotic drug

Melperone is an atypical antipsychotic of the butyrophenone chemical class, making it structurally related to the typical antipsychotic haloperidol. It first entered clinical use in 1960s.

<span class="mw-page-title-main">Clopenthixol</span> Antipsychotic medication

Clopenthixol (Sordinol), also known as clopentixol, is a typical antipsychotic drug of the thioxanthene class. It was introduced by Lundbeck in 1961.

<span class="mw-page-title-main">Perospirone</span> Atypical antipsychotic medication

Perospirone (Lullan) is an atypical antipsychotic of the azapirone family. It was introduced in Japan by Dainippon Sumitomo Pharma in 2001 for the treatment of schizophrenia and acute cases of bipolar mania.

<span class="mw-page-title-main">Pimavanserin</span> Atypical antipsychotic medication

Pimavanserin, sold under the brand name Nuplazid, is an atypical antipsychotic which is approved for the treatment of Parkinson's disease psychosis and is also being studied for the treatment of Alzheimer's disease psychosis, schizophrenia, agitation, and major depressive disorder. Unlike other antipsychotics, pimavanserin is not a dopamine receptor antagonist.

<span class="mw-page-title-main">Aripiprazole lauroxil</span> Chemical compound

Aripiprazole lauroxil, sold under the brand name Aristada, is a long-acting injectable atypical antipsychotic that was developed by Alkermes. It is an N-acyloxymethyl prodrug of aripiprazole that is administered via intramuscular injection once every four to eight weeks for the treatment of schizophrenia. Aripiprazole lauroxil was approved by the U.S. Food and Drug Administration (FDA) on 5 October 2015.

References

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  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).