Fluphenazine
Encyclopedia
Fluphenazine is a typical antipsychotic
drug
used for the treatment of psychoses
such as schizophrenia
and acute manic
phases of bipolar disorder
. It belongs to the piperazine
class of phenothiazine
s.
Its main use is as a long acting injection given once every two or three weeks to people with schizophrenia
who suffer frequent relapses of illness. Its side effect profile is similar to haloperidol
, namely predominantly dopamine
-blocking effects which give rise to akathisia
, parkinsonism
and tremor. Long term side effects include the potentially irreversible tardive dyskinesia
and the potentially fatal neuroleptic malignant syndrome
.
flucate
decanoate or 20 mg of flupentixol
decanoate.
, extrapyramidal
side effects, including tardive dyskinesia
and Rabbit syndrome
. The frequency and severity of extrapyramidal side effects are direct proportional to the dose given and the duration of treatment. Mostly notably, although rare, it can cause hypothermia
because it inhibits ability to shiver.
Sedative, allergic-toxic and anticholinergic
/sympatholytic side effects are less likely to occur compared with chlorpromazine
. The direct deposition of fluphenazine in the cornea
and retina
has so far not been reported.
Neuroleptic malignant syndrome
, although rare, is a potentially lethal side effect of all antipsychotics.
and related antipsychotics.
Alkylation of 2-trifluoromethylphenothiazine using 4-formyl-1-piperazineylpropylchloride in the presence of sodamide synthesizes 2-trifluoromethyl-10-[3-(4-formyl-1-piperazinyl)propyl]phenothiazine. Further alkaline hydrolysis
removes the N-formyl group, giving 2-trifluoromethyl-10-[3-(1-piperazinyl)propyl]phenothiazine. This is alkylated by 2-bromoethanol-1 acetate, which upon further acidic hydrolysis removes the protecting acetyl group, yielding fluphenazine.
Typical antipsychotic
Typical antipsychotics are a class of antipsychotic drugs first developed in the 1950s and used to treat psychosis...
drug
Medication
A pharmaceutical drug, also referred to as medicine, medication or medicament, can be loosely defined as any chemical substance intended for use in the medical diagnosis, cure, treatment, or prevention of disease.- Classification :...
used for the treatment of psychoses
Psychosis
Psychosis means abnormal condition of the mind, and is a generic psychiatric term for a mental state often described as involving a "loss of contact with reality"...
such as schizophrenia
Schizophrenia
Schizophrenia is a mental disorder characterized by a disintegration of thought processes and of emotional responsiveness. It most commonly manifests itself as auditory hallucinations, paranoid or bizarre delusions, or disorganized speech and thinking, and it is accompanied by significant social...
and acute manic
Manic
Manić is a suburban settlement of Belgrade, the capital of Serbia. It is located in the municipality of Barajevo.Manić developed on the eastern slopes of the Kosmaj mountain...
phases of bipolar disorder
Bipolar disorder
Bipolar disorder or bipolar affective disorder, historically known as manic–depressive disorder, is a psychiatric diagnosis that describes a category of mood disorders defined by the presence of one or more episodes of abnormally elevated energy levels, cognition, and mood with or without one or...
. It belongs to the piperazine
Piperazine
Piperazine is an organic compound that consists of a six-membered ring containing two opposing nitrogen atoms. Piperazine exists as small alkaline deliquescent crystals with a saline taste....
class of phenothiazine
Phenothiazine
Phenothiazine is an organic compound that occurs in various antipsychotic and antihistaminic drugs. It has the formula S2NH. This yellow tricyclic compound is soluble in acetic acid, benzene, and ether. The compound is related to the thiazine-class of heterocyclic compounds...
s.
Its main use is as a long acting injection given once every two or three weeks to people with schizophrenia
Schizophrenia
Schizophrenia is a mental disorder characterized by a disintegration of thought processes and of emotional responsiveness. It most commonly manifests itself as auditory hallucinations, paranoid or bizarre delusions, or disorganized speech and thinking, and it is accompanied by significant social...
who suffer frequent relapses of illness. Its side effect profile is similar to haloperidol
Haloperidol
Haloperidol is a typical antipsychotic. It is in the butyrophenone class of antipsychotic medications and has pharmacological effects similar to the phenothiazines....
, namely predominantly dopamine
Dopamine
Dopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this substituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D1, D2, D3, D4, and D5—and their...
-blocking effects which give rise to akathisia
Akathisia
Akathisia, or acathisia, is a syndrome characterized by unpleasant sensations of inner restlessness that manifests itself with an inability to sit still or remain motionless...
, parkinsonism
Parkinsonism
Parkinsonism is a neurological syndrome characterized by tremor, hypokinesia, rigidity, and postural instability. The underlying causes of parkinsonism are numerous, and diagnosis can be complex...
and tremor. Long term side effects include the potentially irreversible tardive dyskinesia
Tardive dyskinesia
Tardive dyskinesia is a difficult-to-treat form of dyskinesia that can be tardive...
and the potentially fatal neuroleptic malignant syndrome
Neuroleptic malignant syndrome
Neuroleptic malignant syndrome is a life- threatening neurological disorder most often caused by an adverse reaction to neuroleptic or antipsychotic drugs...
.
Brand names
| Fluphenazine decanoate: | Modecate, Prolixin Decanoate, Dapotum D, Anatensol, Fludecate, Sinqualone Deconoate |
| Fluphenazine enanthate: | Dapotum Injektion, Flunanthate, Moditen Enanthate Injection, Sinqualone Enanthate |
| Fluphenazine hydrochloride Hydrochloride In chemistry, hydrochlorides are salts resulting, or regarded as resulting, from the reaction of hydrochloric acid with an organic base . This is also known as muriate, derived from hydrochloric acid's other name: muriatic acid.... : |
Prolixin, Permitil, Dapotum, Lyogen, Moditen, Omca, Sediten, Selecten, Sevinol, Sinqualone, Trancin |
Pharmacokinetics
Fluphenazine has an incomplete oral bioavailability of 40% to 50% (due to extensive first pass metabolization in the liver). Its half life is 15 to 30 hours.Dosing
12.5 mg of fluphenazine decanoate is roughly equivalent to 100 mg of zuclopenthixolZuclopenthixol
Zuclopenthixol , also known as zuclopentixol, is a typical antipsychotic drug of the thioxanthene class...
decanoate or 20 mg of flupentixol
Flupentixol
Flupentixol , also known as flupenthixol , marketed under brand names such as Depixol and Fluanxol, is a typical antipsychotic drug of the thioxanthene class...
decanoate.
Side effects
Notable side effects include akathisiaAkathisia
Akathisia, or acathisia, is a syndrome characterized by unpleasant sensations of inner restlessness that manifests itself with an inability to sit still or remain motionless...
, extrapyramidal
Extrapyramidal symptoms
The extrapyramidal system can be affected in a number of ways, which are revealed in a range of extrapyramidal symptoms , also known as extrapyramidal side-effects , such as akinesia and akathisia .Extrapyramidal symptoms are various movement disorders such as acute dystonic reactions,...
side effects, including tardive dyskinesia
Tardive dyskinesia
Tardive dyskinesia is a difficult-to-treat form of dyskinesia that can be tardive...
and Rabbit syndrome
Rabbit syndrome
Rabbit syndrome is a rare form of extrapyramidal side effect of antipsychotic drugs in which perioral tremors occur at a rate of 5 Hz. Rabbit syndrome is characterized by involuntary, fine, rhythmic motions of the mouth along a vertical plane, without involvement of the tongue...
. The frequency and severity of extrapyramidal side effects are direct proportional to the dose given and the duration of treatment. Mostly notably, although rare, it can cause hypothermia
Hypothermia
Hypothermia is a condition in which core temperature drops below the required temperature for normal metabolism and body functions which is defined as . Body temperature is usually maintained near a constant level of through biologic homeostasis or thermoregulation...
because it inhibits ability to shiver.
Sedative, allergic-toxic and anticholinergic
Anticholinergic
An anticholinergic agent is a substance that blocks the neurotransmitter acetylcholine in the central and the peripheral nervous system. An example of an anticholinergic is dicycloverine, and the classic example is atropine....
/sympatholytic side effects are less likely to occur compared with chlorpromazine
Chlorpromazine
Chlorpromazine is a typical antipsychotic...
. The direct deposition of fluphenazine in the cornea
Cornea
The cornea is the transparent front part of the eye that covers the iris, pupil, and anterior chamber. Together with the lens, the cornea refracts light, with the cornea accounting for approximately two-thirds of the eye's total optical power. In humans, the refractive power of the cornea is...
and retina
Retina
The vertebrate retina is a light-sensitive tissue lining the inner surface of the eye. The optics of the eye create an image of the visual world on the retina, which serves much the same function as the film in a camera. Light striking the retina initiates a cascade of chemical and electrical...
has so far not been reported.
Neuroleptic malignant syndrome
Neuroleptic malignant syndrome
Neuroleptic malignant syndrome is a life- threatening neurological disorder most often caused by an adverse reaction to neuroleptic or antipsychotic drugs...
, although rare, is a potentially lethal side effect of all antipsychotics.
Chemistry
Fluphenazine (4-[3-[2-(trifluoromethyl)phenothiazin-10-yl]propyl]-1-piperazineethanol), is synthesized by any of the methods described already for the preparation of trifluoperazineTrifluoperazine
Trifluoperazine is a typical antipsychotic of the phenothiazine chemical class.- Uses :...
and related antipsychotics.
- G.E. Ullyot, (1962).
- R.C. Merril, H.L. Yale, (1963).
- Smith Kline & French Lab., (1960).
- Sherico Ltd., (1960).
- R.C. Merril, H.L. Yale, (1965).
- E.L. Anderson, G.B. Bellizona, P.N. Craig, G.E. Jaffe, K.P. Janewaes, C. Kaiser, B.M. Hester, E.J. Nikawitz, A. Pavloff, H.E. Reift, Ch.L. Zirkle, Arzneim.-Forsch., 12, 937 (1962).
Alkylation of 2-trifluoromethylphenothiazine using 4-formyl-1-piperazineylpropylchloride in the presence of sodamide synthesizes 2-trifluoromethyl-10-[3-(4-formyl-1-piperazinyl)propyl]phenothiazine. Further alkaline hydrolysis
Hydrolysis
Hydrolysis is a chemical reaction during which molecules of water are split into hydrogen cations and hydroxide anions in the process of a chemical mechanism. It is the type of reaction that is used to break down certain polymers, especially those made by condensation polymerization...
removes the N-formyl group, giving 2-trifluoromethyl-10-[3-(1-piperazinyl)propyl]phenothiazine. This is alkylated by 2-bromoethanol-1 acetate, which upon further acidic hydrolysis removes the protecting acetyl group, yielding fluphenazine.
- E.L. Anderson, G.B. Bellizona, P.N. Craig, G.E. Jaffe, K.P. Janewaes, C. Kaiser, B.M. Hester, E.J. Nikawitz, A. Pavloff, H.E. Reift, Ch.L. Zirkle, Arzneim.-Forsch., 12, 937 (1962).
- J.W. Cusic, (1956).