Trifluoperazine

Trifluoperazine (Eskazinyl, Eskazine, Jatroneural, Modalina, Stelazine, Terfluzine, Trifluoperaz, Triftazin) is a typical antipsychotic of the phenothiazine chemical class.

Uses
The primary application of trifluoperazine is for schizophrenia. 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 For most patients with AD, withdrawal of neuroleptics had no overall detrimental effect on functional and cognitive status and by some measures improved functional and cognitive status. Neuroleptics may have some value in the maintenance treatment of more severe neuropsychiatric symptoms, but this possibility must be weighed against the unwanted effects of therapy. The current study helps to inform a clinical management strategy for current practice, but the considerable risks of maintenance therapy highlight the urgency of further work to find, develop, and implement safer and more effective treatment approaches for neuropsychiatric symptoms in people with AD.

Pharmacology
Trifluoperazine has central antiadrenergic, antidopaminergic, and minimal anticholinergic effects. It is believed to work by blockading dopamine D1 and D2 receptors in the mesocortical and mesolimbic pathways, relieving or minimizing such symptoms of schizophrenia as hallucinations, delusions, and disorganized thought and speech.

Side effects
A 2004 meta-analysis 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.

Contraindications
Trifluoperazine is contraindicated in CNS depression, coma, and blood dyscrasias. Trifluoperazine should be used with caution in patients suffering from renal or hepatic impairment.

Formulations
In the United Kingdom 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. Both combinations are not available any longer.

In Italy 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 prochlorperazine, 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).
 * P.N. Craig, G.E. Ullyot, (1956).
 * B.H. Chung, F. Zimalkowski, Arch. Pharm., 317, 323 (1984).