Trifluoperazine
Encyclopedia
Trifluoperazine is a typical antipsychotic
of the phenothiazine
chemical class.
. Other official indications may vary country by country, but generally it is also indicated for use in agitation and patients with behavioural problems, severe nausea
and vomiting as well as severe anxiety. Its use in many parts of the world has declined because of highly frequent and severe early and late tardive dyskinesia
, a type of extrapyramidal symptom. The annual development rate of tardive dyskinesia may be as high as 4%.
A 2006 study suggested that trifluoperazine may be able to reverse addiction to opioids.
A multi-year UK study by the Alzheimer's Research Trust suggested that this and other antipsychotic
drugs commonly given to Alzheimer's patients with mild behavioural problems often make their condition worse. The study concluded that
effects. It is believed to work by blockading dopamine D1
and D2
receptors in the mesocortical
and mesolimbic pathway
s, relieving or minimizing such symptoms of schizophrenia as hallucination
s, delusion
s, and disorganized thought and speech.
of the studies on trifluoperazine found that it is more likely than placebo to cause extrapyramidal side effects such as akathisia
, dystonia
, and Parkinsonism
. It is also more likely to cause somnolence
and anticholinergic side effects such as blurred vision
and xerostomia
(dry mouth). All phenothiazines can cause the rare and sometimes fatal neuroleptic malignant syndrome
. Trifluoperazine can lower the seizure threshold. The antimuscarinic action of trifluoperazine can cause excessive dilation of the pupils (mydriasis
), which increases the chances of patients with hyperopia
developing glaucoma
.
, coma
, and blood dyscrasias. Trifluoperazine should be used with caution in patients suffering from renal or hepatic impairment.
and some other countries, Trifluoperazine is sold and marketed under the brand 'Stelazine'.
The drug is sold as tablet, liquid and 'Trifluoperazine-injectable USP' for deep intramuscular short-term use.
In the past, trifluoperazine was used in fixed combinations with the MAO inhibitor (antidepressant) tranylcypromine
to attenuate the strong stimulating effects of this antidepressant. This combination was sold under the brand name Jatrosom N. Likewise a combination with amobarbital
(potent sedative/hypnotic agent) for the amelioration of psychoneurosis and insomnia
existed under the brand name Jalonac. In Italy
the first combination is still available, sold under the brand name Parmodalin (10 mg of Tranylcypromine and 1 mg of Trifluoperazine).
, alkylation is performed using 2-trifluoromethylphenothazin-4-methyl-1-piperazinylpropylchloride as the substrate.
Typical antipsychotic
Typical antipsychotics are a class of antipsychotic drugs first developed in the 1950s and used to treat psychosis...
of the 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...
chemical class.
Uses
The primary application of trifluoperazine is for schizophreniaSchizophrenia
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...
. Other official indications may vary country by country, but generally it is also indicated for use in agitation and patients with behavioural problems, severe nausea
Nausea
Nausea , is a sensation of unease and discomfort in the upper stomach with an involuntary urge to vomit. It often, but not always, precedes vomiting...
and vomiting as well as severe anxiety. Its use in many parts of the world has declined because of highly frequent and severe early and late tardive dyskinesia
Tardive dyskinesia
Tardive dyskinesia is a difficult-to-treat form of dyskinesia that can be tardive...
, a type of extrapyramidal symptom. The annual development rate of tardive dyskinesia may be as high as 4%.
A 2006 study suggested that trifluoperazine may be able to reverse addiction to opioids.
A multi-year UK study by the Alzheimer's Research Trust suggested that this and other antipsychotic
Antipsychotic
An antipsychotic is a tranquilizing psychiatric medication primarily used to manage psychosis , particularly in schizophrenia and bipolar disorder. A first generation of antipsychotics, known as typical antipsychotics, was discovered in the 1950s...
drugs commonly given to Alzheimer's patients with mild behavioural problems often make their condition worse. The study concluded that
Pharmacology
Trifluoperazine has central antiadrenergic, antidopaminergic, and minimal anticholinergicAnticholinergic
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....
effects. It is believed to work by blockading dopamine D1
Dopamine receptor D1
Dopamine receptor D1, also known as DRD1, is a protein that in humans is encoded by the DRD1 gene.- Function :This gene encodes the D1 subtype of the dopamine receptor. The D1 subtype is the most abundant dopamine receptor in the central nervous system. This G-protein-coupled receptor stimulates...
and D2
Dopamine receptor D2
Dopamine receptor D2, also known as D2R, is a protein that, in humans, is encoded by the DRD2 gene.- Function :This gene encodes the D2 subtype of the dopamine receptor. This G protein-coupled receptor inhibits adenylyl cyclase activity...
receptors in the mesocortical
Mesocortical pathway
The mesocortical pathway is a neural pathway that connects the ventral tegmentum to the cerebral cortex, particularly the frontal lobes. It is one of the four major dopamine pathways in the brain...
and mesolimbic pathway
Mesolimbic pathway
The mesolimbic pathway is one of the dopaminergic pathways in the brain. The pathway begins in the ventral tegmental area of the midbrain and connects to the limbic system via the nucleus accumbens, the amygdala, and the hippocampus as well as to the medial prefrontal cortex...
s, relieving or minimizing such symptoms of schizophrenia as hallucination
Hallucination
A hallucination, in the broadest sense of the word, is a perception in the absence of a stimulus. In a stricter sense, hallucinations are defined as perceptions in a conscious and awake state in the absence of external stimuli which have qualities of real perception, in that they are vivid,...
s, delusion
Delusion
A delusion is a false belief held with absolute conviction despite superior evidence. Unlike hallucinations, delusions are always pathological...
s, and disorganized thought and speech.
Side effects
A 2004 meta-analysisMeta-analysis
In statistics, a meta-analysis combines the results of several studies that address a set of related research hypotheses. In its simplest form, this is normally by identification of a common measure of effect size, for which a weighted average might be the output of a meta-analyses. Here the...
of the studies on trifluoperazine found that it is more likely than placebo to cause extrapyramidal side effects such as 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...
, dystonia
Dystonia
Dystonia is a neurological movement disorder, in which sustained muscle contractions cause twisting and repetitive movements or abnormal postures. The disorder may be hereditary or caused by other factors such as birth-related or other physical trauma, infection, poisoning or reaction to...
, and 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...
. It is also more likely to cause somnolence
Somnolence
Somnolence is a state of near-sleep, a strong desire for sleep, or sleeping for unusually long periods . It has two distinct meanings, referring both to the usual state preceding falling asleep, and the chronic condition referring to being in that state independent of a circadian rhythm...
and anticholinergic side effects such as blurred vision
Blurred vision
-Causes:There are many causes of blurred vision:* Use of atropine or other anticholinergics* Presbyopia -- Difficulty focusing on objects that are close. The elderly are common victims....
and xerostomia
Xerostomia
Xerostomia is the medical term for the subjective complaint of dry mouth due to a lack of saliva. Xerostomia is sometimes colloquially called pasties, cottonmouth, drooth, or doughmouth. Several diseases, treatments, and medications can cause xerostomia. It can also be exacerbated by smoking or...
(dry mouth). All phenothiazines can cause the rare and sometimes 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...
. Trifluoperazine can lower the seizure threshold. The antimuscarinic action of trifluoperazine can cause excessive dilation of the pupils (mydriasis
Mydriasis
Mydriasis is a dilation of the pupil due to disease, trauma or the use of drugs. Normally, the pupil dilates in the dark and constricts in the light to respectively improve vividity at night and to protect the retina from sunlight damage during the day...
), which increases the chances of patients with hyperopia
Hyperopia
Hyperopia, also known as farsightedness, longsightedness or hypermetropia, is a defect of vision caused by an imperfection in the eye , causing difficulty focusing on near objects, and in extreme cases causing a sufferer to be unable to focus on objects at any distance...
developing glaucoma
Glaucoma
Glaucoma is an eye disorder in which the optic nerve suffers damage, permanently damaging vision in the affected eye and progressing to complete blindness if untreated. It is often, but not always, associated with increased pressure of the fluid in the eye...
.
Contraindications
Trifluoperazine is contraindicated in CNS depressionCNS depression
Central nervous system depression or CNS depression refers to physiological depression of the central nervous system that can result in decreased rate of breathing, decreased heart rate, and loss of consciousness possibly leading to coma or death...
, coma
Coma
In medicine, a coma is a state of unconsciousness, lasting more than 6 hours in which a person cannot be awakened, fails to respond normally to painful stimuli, light or sound, lacks a normal sleep-wake cycle and does not initiate voluntary actions. A person in a state of coma is described as...
, and blood dyscrasias. Trifluoperazine should be used with caution in patients suffering from renal or hepatic impairment.
Formulations
In the United KingdomUnited Kingdom
The United Kingdom of Great Britain and Northern IrelandIn the United Kingdom and Dependencies, other languages have been officially recognised as legitimate autochthonous languages under the European Charter for Regional or Minority Languages...
and some other countries, Trifluoperazine is sold and marketed under the brand 'Stelazine'.
The drug is sold as tablet, liquid and 'Trifluoperazine-injectable USP' for deep intramuscular short-term use.
In the past, trifluoperazine was used in fixed combinations with the MAO inhibitor (antidepressant) tranylcypromine
Tranylcypromine
Tranylcypromine is a drug of the substituted phenethylamine and amphetamine classes which acts as a monoamine oxidase inhibitor —it is a non-selective and irreversible inhibitor of the enzyme monoamine oxidase...
to attenuate the strong stimulating effects of this antidepressant. This combination was sold under the brand name Jatrosom N. Likewise a combination with amobarbital
Amobarbital
Amobarbital is a drug that is a barbiturate derivative. It has sedative-hypnotic and analgesic properties. It is a white crystalline powder with no odor and a slightly bitter taste. It was first synthesized in Germany in 1923...
(potent sedative/hypnotic agent) for the amelioration of psychoneurosis and insomnia
Insomnia
Insomnia is most often defined by an individual's report of sleeping difficulties. While the term is sometimes used in sleep literature to describe a disorder demonstrated by polysomnographic evidence of disturbed sleep, insomnia is often defined as a positive response to either of two questions:...
existed under the brand name Jalonac. In Italy
Italy
Italy , officially the Italian Republic languages]] under the European Charter for Regional or Minority Languages. In each of these, Italy's official name is as follows:;;;;;;;;), is a unitary parliamentary republic in South-Central Europe. To the north it borders France, Switzerland, Austria and...
the first combination is still available, sold under the brand name Parmodalin (10 mg of Tranylcypromine and 1 mg of Trifluoperazine).
Chemistry
Trifluoperazine (2-trifluoromethyl-10-[3-(4-methyl-1-piperazinyl)propyl]phenothazine) is synthesized in the manner described already for prochlorperazineProchlorperazine
Prochlorperazine is a dopamine receptor antagonist that belongs to the phenothiazine class of antipsychotic agents that are used for the antiemetic treatment of nausea and vertigo. It is also a highly-potent typical antipsychotic, 10-20x more potent than chlorpromazine...
, alkylation is performed using 2-trifluoromethylphenothazin-4-methyl-1-piperazinylpropylchloride as the substrate.
- G.E. Ullyot, (1960).
- P.N. Craig, G.E. Ullyot, (1956).
- B.H. Chung, F. Zimalkowski, Arch. Pharm., 317, 323 (1984).