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Trifluoperazine

Trifluoperazine (Eskazinyl^®, Eskazine^®, Jatroneural^®, Modalina^®, Stelazine^®, Terfluzine^®) is a typical antipsychotic drug of the phenothiazine group. Trifluoperazine is a highly potent drug (approx. 20-times more potent than Chlorpromazine). more...

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Pharmakokinetics

Little is known about human pharmacokinetics. One study has the following results: A study of the pharmacokinetics of trifluoperazine as a single 5-mg dose by mouth in 5 healthy subjects. Peak plasma concentrations of trifluoperazine were reached from 1.5 to 4.5 hours after ingestion and varied widely between subjects, ranging from 0.53 to 3.09 ng per mL. Elimination of trifluoperazine was multiphasic; the mean elimination half-life was estimated to be 5.1 hours over the period from 4.5 to 12 hours after ingestion, while the mean apparent terminal elimination half-life was estimated to be 12.5 hours

Uses

The primarary indication of trifluoperazine is schizophrenia. Its use in many parts of the world has declined because of highly frequent and severe early and late (tardive dyskinesia) extrapyramidal symptoms. The annual development rate of tardive dyskinesia may be as high as 4%.

Side Effects

Also, all side-effects of chlorpromazine may occur. These are sedative, hypotensive, anticholinergic/sympatholytic and allergic-toxic ones. A partiular severe form of liver damage has been reported. Therefore, preexisting liver damage is a clear contraindication.

Formulations

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®. Likeweise a combination with amobarbital (strong sedative/hypnotic agent) for the amelioration of psychoneurosis and insomnia existed under the brand name Jalonac®. Both combinations are not available any longer.

The drug is sold as tablet, liquid and 'Trifluperazine-injectable USP' for deep IM short-term use.

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Quaternary structure built from subunits combining NMR and small-angle X-Ray scattering data
From Biophysical Journal, 8/1/02 by Mattinen, Maija-Liisa

ABSTRACT A new principle in constructing molecular complexes from the known high-resolution domain structures joining data from NMR and small-angle x-ray scattering (SAXS) measurements is described. Structure of calmodulin in complex with trifluoperazine was built from N- and C-terminal domains oriented based on residual dipolar couplings measured by NMR in a dilute liquid crystal, and the overall shape of the complex was derived from SAXS data. The residual dipolar coupling data serves to reduce angular degrees of freedom, and the small-angle scattering data serves to confine the translational degrees of freedom. The complex built by this method was found to be consistent with the known crystal structure. The study demonstrates how approximate tertiary structures of modular proteins or quaternary structures composed of subunits can be assembled from high-resolution structures of domains or subunits using mutually complementary NMR and SAXS data.

INTRODUCTION

We are indebted to Andrea Hounslow and Clare Treritt for advice and assistance.

This work was supported by the Academy of Finland and Technology Agent of Finland (TEKES).

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Maija-Liisa Mattinen,* Kimmo Paakkonen,* Teemu Ikonen,^ Jeremy Craven,^^ Torbjorn Drakenberg,* Ritva Serimaa,^ Jonathan Waltho,^^ and Arto Annila^

*VTT Biotechnology, FIN-02044 VTT, Espoo, Finland; ^Department of Physical Sciences, University of Helsinki, FIN-00014 Helsinki, Finland; and ^^Department of Molecular Biology and Biotechnology, University of Sheffield, Sheffield S10 2TN, United Kingdom

Submitted October 31, 2001, and accepted for publication February 19, 2002.

Address reprint requests to Dr. Arto Annila, Institute of Biotechnology, University of Helsinki, P.O. Box 56, FIN-00014 Helsinki, Finland. Tel.: 358-9-191-50629; Fax: 358-9-191-50639; E-mail: arto.annila@helsinki.fi.

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