Penfluridol (Semap, Micefal, Longoperidol) is a highly potent, first generation

diphenylbutylpiperidine Diphenylbutylpiperidines are a class of typical antipsychotic drugs which were all synthesized, developed, and marketed by Janssen Pharmaceutica. They include: * Clopimozide (R-29,764) * Fluspirilene (Redeptin) * Penfluridol (Semap, Micefal, Lon ...

antipsychotic Antipsychotics, also known as neuroleptics, are a class of Psychiatric medication, psychotropic medication primarily used to manage psychosis (including delusions, hallucinations, paranoia or disordered thought), principally in schizophrenia but ...

. It was discovered at

Janssen Pharmaceutica Janssen Pharmaceuticals is a pharmaceutical company headquartered in Beerse, Belgium, and wholly-owned by Johnson & Johnson. It was founded in 1953 by Paul Janssen. In 1961, Janssen Pharmaceuticals was purchased by New Jersey-based American c ...

in 1968. Related to other diphenylbutylpiperidine antipsychotics,

pimozide Pimozide (sold under the brand name Orap) is an antipsychotic drug of the diphenylbutylpiperidine class. It was discovered at Janssen Pharmaceutica in 1963. It has a high potency compared to chlorpromazine (ratio 50-70:1). On a weight basis i ...

and

fluspirilene Fluspirilene (Redeptin, Imap, R6218) is a diphenylbutylpiperidine typical antipsychotic drug, used for the treatment of schizophrenia. It is administered intramuscularly. It was discovered at Janssen Pharmaceutica in 1963.C. Janssen, NV Res. Lab. ...

, penfluridol has an extremely long elimination half-life and its effects last for many days after single oral dose. Its antipsychotic potency, in terms of dose needed to produce comparable effects, is similar to both

haloperidol Haloperidol, sold under the brand name Haldol among others, is a typical antipsychotic medication. Haloperidol is used in the treatment of schizophrenia, tics in Tourette syndrome, mania in bipolar disorder, delirium, agitation, acute psychosi ...

and pimozide. It is only slightly

sedative A sedative or tranquilliser is a substance that induces sedation by reducing irritability or excitement. They are CNS depressants and interact with brain activity causing its deceleration. Various kinds of sedatives can be distinguished, but t ...

, but often causes extrapyramidal side-effects, such as

akathisia Akathisia is a movement disorder characterized by a subjective feeling of inner restlessness accompanied by mental distress and an inability to sit still. Usually, the legs are most prominently affected. Those affected may fidget, rock back and ...

dyskinesia Dyskinesia refers to a category of movement disorders that are characterized by involuntary muscle movements, including movements similar to tics or chorea and diminished voluntary movements. Dyskinesia can be anything from a slight tremor of t ...

e and pseudo-

Parkinsonism Parkinsonism is a clinical syndrome characterized by tremor, bradykinesia (slowed movements), rigidity, and postural instability. These are the four motor symptoms found in Parkinson's disease (PD), after which it is named, dementia with Lewy bo ...

. Penfluridol is indicated for antipsychotic treatment of chronic

schizophrenia Schizophrenia is a mental disorder characterized by continuous or relapsing episodes of psychosis. Major symptoms include hallucinations (typically hearing voices), delusions, and disorganized thinking. Other symptoms include social withdra ...

and similar

psychotic disorders Psychosis is a condition of the mind that results in difficulties determining what is real and what is not real. Symptoms may include delusions and hallucinations, among other features. Additional symptoms are incoherent speech and behavior t ...

, it is, however, like most typical antipsychotics, being increasingly replaced by the

atypical antipsychotics The atypical antipsychotics (AAP), also known as second generation antipsychotics (SGAs) and serotonin–dopamine antagonists (SDAs), are a group of antipsychotic drugs (antipsychotic drugs in general are also known as major tranquilizers and ne ...

. Due to its extremely long-lasting effects, it is often prescribed to be taken orally as tablets only once a week (q 7 days). The once-weekly dose is usually 10–60 mg. A 2006

systematic review A systematic review is a Literature review, scholarly synthesis of the evidence on a clearly presented topic using critical methods to identify, define and assess research on the topic. A systematic review extracts and interprets data from publ ...

examined the use of penfluridol for people with schizophrenia:

Synthesis

The

Grignard reaction The Grignard reaction () is an organometallic chemical reaction in which alkyl, allyl, vinyl, or aryl-magnesium halides ( Grignard reagent) is added to a carbonyl group in an aldehyde or ketone. This reaction is important for the formation of ...

between Methyl 4-oxopiperidine-1-carboxylate 9976-54-3(1) and 5-bromo-2-chlorobenzotrifluoride 45-01-2(2) gives methyl 4- -chloro-3-(trifluoromethyl)phenyl4-hydroxypiperidine-1-carboxylate
CID:134990265
(3). Deprotection of the urethane gives 4- -Chloro-3-(trifluoromethyl)phenyl4-piperidinol 1928-50-7(4). Lastly alkylation with 1,1'-(4-Chlorobutylidene)bis(4-fluorobenzene) 312-04-7(5) completed the synthesis of Penfluridol (6).

Synthesis

See also

References

Further reading