Pharmacokinetic study in mice of galphimine-A, an anxiolytic compound from Galphimia glauca

Abstract

The aim of this study was to obtain pharmacokinetic data for the anxiolytic compound galphimine-A (G-A) from Galphimia glauca. G-A is the most abundant anxiolytic compound in this plant, while Galphimine-E (G-E) is the most abundant galphimine, but inactive. G-E was transformed chemically into G-A. The pharmacokinetic study was carried out in ICR mice, which were orally administered a single 200 mg/kg dose of G-A. Samples of blood and brain were taken at different times after administration of G-A. Previously, we established the validation of methods for determining the concentration of G-A. The G-A was detected in plasma 5 min after oral administration, and its concentration reached 2.47 μg/mL. Data from concentration-time curves allowed us to establish the main pharmacokinetic parameters in two models: one- and/or two-compartment. C(max) values were 3.33 and 3.42 μg/mL respectively, likewise AUC(0→1440 min) were 1,951.58 and 1,824.95 μg/mL·min. The G-A in brain tissue was noted to cross the blood-brain barrier, reaching C(max) 2.74 μg/mL, T(max) 81.6 min, and then drop gradually to 0.32 μg/mL detected at 24 h. The presence of G-A in brain tissue, confirmed that this anxiolytic compound can access the target organ and acts directly on the CNS.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1

Chemical structure of galphimines: (1) G–A, (2) G–E.

Figure 2

HPLC chromatograms for galphimine-A (G–A), which represent the process of production, purification and validation of process of quantitation of both plasma and brain. The analyses were performed in a Waters 2695 HPLC. A Cromotith Performace® RP-18e column (100 mm × 4.6 mm) was used and operated a 25 °C. The mobile phase consisted of acetonitrile:water (35:65, 1 mL/min). Panel (a) and (b), show the monitoring of the transformation of G–E (RT = 8.29 min) to G–A (RT = 7.12 min). The chromatogram (c) shows the untreated mouse plasma. The chromatograms displayed in panels (d), (e), (f) and (g), show the internal standard peak and galphimine-A in decreasing concentration in plasma (62.5, 15.62, 3.9 y 0.97 µg/mL). The retention times were about 5.5 and 7.2 respectively. The chromatograms displayed panels (h), (i) and (j), showing the internal standard peak and galphimine-A in brain homogenate (12.5, 3.12 and 0.78 µg/mL). The retention times were again about 5.5 and 7.2 respectively.

Figure 3

Concentration-time curve of galphimine A in plasma. The experimental data (○) and estimates of the application of one-compartment () and two-compartment (-----) models.