Tissue Metabolites of Trifluoperazine, Fluphenazine, Prochlorperazine, and Perphenazine in the Rat: Identification and Synthesis

Breyer, Ursula; Prox, A.; Bertele, Rudolf; Gaertner, H. J.

doi:10.1002/jps.2600631204

Cited by 16 publications

(3 citation statements)

References 8 publications

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“…This can be explained by the occurrence of CF3-PER as the dihydrochloride, while CF3-PER-OH and CF3-PER-SO were available as free bases. 27 This was demonstrated by additional NMR measurements in DMSO-d 6 in which the ammonium proton H-7 0 at 12.15 ppm of CF3-PER was observable. In solution, protonation of N-4 0 was never observed.…”

Section: Analysis Of Test Mixturesmentioning

confidence: 83%

Identification of trifluoperazine metabolites using HPLC-NMR of test mixtures

et al. 2000

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The metabolites of the antipsychotic drug trifluoperazine (TFP) were investigated with on‐line coupling of high‐performance liquid chromatography (HPLC) and NMR spectroscopy. A chromatographic method was developed using a reversed‐phase C30 silica gel column. Rats were given a cumulative dose of 90 mg kg−1 TFP dihydrochloride and samples of brain and muscle tissues were extracted after 29 h. The peaks obtained on chromatographic separation were assigned to trifluoperazine and its metabolites. With the help of chromatograms obtained from test mixtures, 1D and 2D HPLC–NMR were used to identify the peaks found for these mixtures. Copyright © 2000 John Wiley & Sons, Ltd.

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Section: Analysis Of Test Mixturesmentioning

confidence: 83%

Identification of trifluoperazine metabolites using HPLC-NMR of test mixtures

et al. 2000

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“…Their occurrence in several pharmaceutically active compounds such as promethazine, prochlorperazine, chlorpromazine, and many antipsychotic drugs is a testament to their growing importance in various fields of research (Figure ). − Synthetic methodologies for the construction and functionalization of phenothiazine are well explored in literature studies − and have helped promote the development of phenothiazine-based functional materials.…”

Section: Introductionmentioning

confidence: 99%

Phenothiazine-Based Cu(II)-Selective Fluorescent Sensor: GHK-Cu Sensing Applications

Sahu,

Yadav,

Gunturu

et al. 2023

J. Org. Chem.

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Sensing important metals in different environments is an important area and involves the development of a wide variety of metal-sensing materials. The employment of fluorescent sensors in metal sensing has been one of the most widely applied methodologies, and the identification of selective metal sensors is important. We herein report a phenothiazine-based Cu(II) fluorescent sensor that is highly selective to Cu(II) ions compared with other transition metal salts. The Lewis acidity of the Cu(II) salt certainly was found to be a factor for obtaining an enhanced sensing response in MeOH as the solvent, while a ratio of 1:1 was calculated to be the most optimum for getting the desired response.

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“…The metabolism of FLU is complex. It is metabolized extensively by aromatic hydroxylation, S-and N-oxidation, N-desalkylation, and glucuronidation (Ebert and Hess 1965;Dreyfuss and Cohen 1971;Breyer et al 1974aBreyer et al , 1974bGaertner et al 1974Gaertner et al , 1975Curry et al 1979). The sulfoxide (FLU-SO), N 4 '-oxide (FLU-NO) and 7-hydroxy (7-OH-FLU) metabolites of FLU ( Figure 1) are found in substantial levels in the plasma of patients treated with PO or IM preparations of FLU (Marder et al 1989).…”

mentioning

confidence: 99%

Distribution of Fluphenazine and Its Metabolites in Brain Regions and Other Tissues of the Rat

Aravagiri

Marder

Yuwiler

et al. 1995

Neuropsychopharmacology

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Rats were given 5, 10, or 20 mg/kg oral doses of fluphenazine (FLU) dihydrochloride daily for 15 days. FLU and its sulfoxide (FL-SO), 7-hydroxy (7-OH-FLU) and N4'-oxide (FLU-NO) metabolites were assayed in plasma, liver, kidney, fat, whole brain, and brain regions by specific and sensitive radioimmunoassays (RIA). All metabolites were detected in tissues at higher levels than in plasma, and the levels increased with dose. FLU was 10- to 27-fold higher in brain regions than in plasma. Brain vs plasma levels of FLU correlated more closely than levels of its metabolites. Liver contained the highest levels of all analytes at all doses. FLU-SO was the major metabolite in brain regions (24% to 96% of FLU) and accumulated in fat 43 to 75 times more than FLU. Levels of 7-OH-FLU and FLU-NO were very low in brain (1% to 20% of FLU). FLU-SO and FLU-NO had only 1% to 3% the affinity for D1 and D2 receptors, but 7-OH-FLU had 20% the D2 and 5% the D1 affinity of FLU. The low affinity for dopamine receptors and low brain-levels of metabolites of FLU indicate that they are not likely to contribute importantly to pharmacologic responses of FLU. Also, the estimated relative "activity factor" for these compounds in the brain indicated that the contribution to neuropharmacologic activity by metabolites is less than 1% of FLU. Consequently, clinical monitoring of plasma FLU alone may be sufficient.

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Tissue Metabolites of Trifluoperazine, Fluphenazine, Prochlorperazine, and Perphenazine in the Rat: Identification and Synthesis

Cited by 16 publications

References 8 publications

Identification of trifluoperazine metabolites using HPLC-NMR of test mixtures

Identification of trifluoperazine metabolites using HPLC-NMR of test mixtures

Phenothiazine-Based Cu(II)-Selective Fluorescent Sensor: GHK-Cu Sensing Applications

Distribution of Fluphenazine and Its Metabolites in Brain Regions and Other Tissues of the Rat

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