In vivo¹⁹F nuclear magnetic resonance spectroscopy of trifluorinated neuroleptics in the rat

Abstract

In vivo 19F NMR measurements of trifluorinated neuroleptics in the rat brain were made using a 13 x 18 mm surface coil at 4.7 T. The signal of fluphenazine was obtained within 8-15 min from brains of living rats treated chronically with drug doses of 5-30 mg/kg. Following the intravenous injection of a single dose of trifluoperazine (30 mg/kg), brain levels could be monitored with a time resolution of 30 min. The data demonstrate the possibility of obtaining in vivo pharmacokinetics of fluorinated agents in the rat brain. 19F NMR is expected to become an important tool in neurochemical research.

Computational analysis of transcriptome signature repurposes low dose trifluoperazine for the treatment of fragile X syndrome in mouse model

“…1d, Supplementary Table 4), predicating potential therapeutic value. From the 4 FDA-approved drugs, we chose trifluoperazine, which can effectively cross the blood brain barrier (BBB) 22, 23 and has been used to treat central nervous system disorders, for experimental validation of therapeutic efficacy. The other 3 FDA-approved compounds have been used for cancer chemotherapy and hypertension treatment, respectively, and were not selected for the current study.…”

Detection of psychoactive drugs using19F MR spectroscopy

“…The initial animal experiments and especially the human studies, which centered on antipsychotic agents such as fluphenazine and trifluoperazine were limited by very low signal-to-noise ratios in vivo, even at very high oral doses. However, with this method it was possible to calculate half-life time of the neuroleptic tri-fluoperazine in the brain of a living animal (Albert et al, 1990) and of the neuroleptic melperone (Gtinther and Albert, 1993). Although given doses of neuroleptics were quite high this method may give the opportunity to study the in vivo pharmacokinetic without sacrificing the animals as it is necessary by conventional methods (e.g., HPLC or TLC of the extracted brain tissue).…”

“…The 19F nucleus has a spin of 1/2 and offers the advantages of high sensitivity (83% relative to 1H), 100% natural abundance, and large spectral dispersion (500 ppm). Since several of the commonly used neuroleptics (such as fluphenazine, flupentixol trifluopromazine and trifluoperazine) as well as antidepressants (fluoxetine and fluvoxamine) carry a trifluoromethyl group, 19F MR is considered a promising technique for estimating brain levels of these drugs in vivo (Bartels et al, 1986;Arndt et al, 1988;Albert et al, 1990).…”

Hydrophobicity predicts in vivo 19F magnetic resonance detectability of fluorinated psychiatric drugs: simple test for likely success in clinical pharmacokinetic studies

“…This prompted us to investigate whether drug detectability could be predicted using approaches which could be implemented quickly and inexpensively on widely available analytical equipment, or even computationally. We chose as a test set several fluorinated psychiatric compounds which have been successfully detected in vivo at therapeutic, submillimolar, levels: the antidepressants fluoxetine [ Komoroski et al, 1991[ Komoroski et al, , 1994Renshaw et al, 1992;Karson et al, 1992Karson et al, , 1993Bartels and Albert, 1995;Miner et al, 1995;Strauss et al, 1997;Bolo et al, 2000;Henry et al, 2000;Strauss and Dager, 2001;Strauss et al, 2002;Henry et al, 2005], fluvoxamine [Bartels and Albert, 1995;Strauss et al, 1997Strauss et al, , 1998Strauss et al, , 2002Bolo et al, 2000] and paroxetine [Henry et al, 2000], the anorexic fenfluramine [Christensen et al, 1998], and the neuroleptics trifluoperazine [Bartels et al, 1986[Bartels et al, , 1991Albert et al, 1990;Komoroski et al, 1991;Karson et al, 1992;Bartels and Albert, 1995] and fluphenazine [Bartels et al, 1986;Albert et al, 1990;Durst et al, 1990;Bartels et al, 1991;Bartels and Albert, 1995]. All except paroxetine contain trifluoromethyl groups attached to aromatic rings; paroxetine contains a monofluorophenyl function.…”