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European Journal of Pharmaceutical... Feb 2023Most drugs, especially those with acidic or neutral moieties, are bound to the plasma protein albumin, whereas basic drugs are preferentially bound to human alpha-1-acid...
Most drugs, especially those with acidic or neutral moieties, are bound to the plasma protein albumin, whereas basic drugs are preferentially bound to human alpha-1-acid glycoprotein (AGP). The protein binding of the long-established drugs ephedrine and pseudoephedrine, which are used in the treatment of hypotension and colds, has so far only been studied with albumin. Since in a previous study a stereoselective binding of ephedrine and pseudoephedrine to serum but not to albumin was observed, the aim of this study was to check whether the enantioselective binding behavior of ephedrine and pseudoephedrine, in addition to the derivatives methylephedrine and norephedrine, is due to AGP and to investigate the influence of their different substituents and steric arrangement. Discontinuous ultrafiltration was used for the determination of protein binding. Characterization of ligand-protein interactions of the drugs was obtained by saturation transfer difference nuclear magnetic resonance spectroscopy. Docking experiments were performed to analyze possible ligand-protein interactions. The more basic the ephedrine derivative is, the higher is the affinity to AGP. There was no significant difference in the binding properties between the individual enantiomers and the diastereomers of ephedrine and pseudoephedrine.
Topics: Humans; Ephedrine; Ligands; Orosomucoid; Phenylpropanolamine; Protein Binding; Pseudoephedrine
PubMed: 36402307
DOI: 10.1016/j.ejps.2022.106333 -
Journal of Ethnopharmacology Jan 2023In our previous study, we reported that Ephedra Herb extract (EHE) increased the locomotor activity of mice in the open-field test and reduced the immobility time in the...
ETHNOPHARMACOLOGICAL RELEVANCE
In our previous study, we reported that Ephedra Herb extract (EHE) increased the locomotor activity of mice in the open-field test and reduced the immobility time in the forced swim test. Ephedrine alkaloids (EAs) are thought to be responsible for the adverse effects of Ephedra Herb. However, there are no reports to verify that the adverse effects of Ephedra Herb are caused by the amount of EAs in the herb. Therefore, we investigated whether these adverse effects of EHE are caused by the amounts of ephedrine (Eph) and pseudoephedrine (Pse) in the herbal extract. In a preliminary study of the time course analysis of the open field test, we newly observed that EHE evoked switching from transient sedation to sustained excitement.
AIM OF THE STUDY
We aimed to confirm whether EHE evokes switching from transient sedation to sustained excitement, investigate whether these actions of EHE are caused by the amount of ephedrine (Eph) and pseudoephedrine (Pse) in the herbal extract, and clarify the molecular mechanism of the transient sedative effect.
MATERIALS AND METHODS
The locomotor activity of mice was tested using the open-field test. The immobility times were measured using a forced swim test, and the motor dysfunction in mice was tested using the rotarod test.
RESULTS
EHE, Eph, and Pse induced transient motionlessness between 0 and 15 min after oral administration, however, they did not induce depression-like behavior and motor dysfunction in mice, suggesting that the motionlessness induced by EHE, Eph, or Pse resulted from sedation. The α2a adrenoceptor inhibitor, atipamezole, decreased their sedative effects. Thus, immediately after EHE administration, the transient sedative effect is mediated through the activation of the α2a adrenoreceptor by Eph and Pse. EHE and Eph increased total locomotor activity for 15-120 min after oral administration; however, Pse had no effect. Therefore, the slow-onset and sustained excitatory effects of EHE are mediated by Eph.
CONCLUSIONS
We discovered for the first time that EHE evokes diphasic action by switching from transient sedation to sustained excitement. The transient sedation was evoked by the Eph and Pse in the herbal extract via activation of the α2a adrenoceptor and the sustained excitement was caused by the Eph in the herbal extract.
Topics: Mice; Animals; Ephedra; Ephedrine; Pseudoephedrine; Alkaloids; Plant Extracts; Hypnotics and Sedatives; Receptors, Adrenergic
PubMed: 36240977
DOI: 10.1016/j.jep.2022.115827 -
BMC Chemistry Aug 2022Fexofenadine hydrochloride and pseudoephedrine hydrochloride are prescribed in a combined dosage form for the treatment of allergic rhinitis. In the present work, a...
Application of green first derivative synchronous spectrofluorometric method for quantitative analysis of fexofenadine hydrochloride and pseudoephedrine hydrochloride in pharmaceutical preparation and spiked human plasma.
Fexofenadine hydrochloride and pseudoephedrine hydrochloride are prescribed in a combined dosage form for the treatment of allergic rhinitis. In the present work, a sensitive synchronous fluorescence spectroscopic method was applied in conjunction with first derivative for quantitative estimation of fexofenadine hydrochloride and pseudoephedrine hydrochloride in pure form, pharmaceutical tablets and spiked human plasma. Fexofenadine hydrochloride showed its conventional emission spectrum at 294 nm when excited at 267 nm. On the other hand, pseudoephedrine hydrochloride showed its conventional emission spectra at 286 nm when excited at 261 nm. The fluorescence intensities were greatly enhanced by the use of sodium dodecyl sulphate as a micellar surfactant. Application of the synchronous mode to measure the fluorescence spectra of the above drugs provided sharp narrowing bands, but the overlap was not completely resolved. Derivatization of the synchronous spectra to the first order completely resolved the overlap of the fluorescence spectra and allowed simultaneous quantitative determination of the drugs under study. Fexofenadine hydrochloride and pseudoephedrine hydrochloride could be determined from their first-order synchronous spectra at 286 and 294 nm, respectively, without interfering with each other. The method showed linearity with an excellent correlation coefficient in the concentration range of 100-1500 ng/mL for Fexofenadine hydrochloride and 50-1000 ng/mL for pseudoephedrine hydrochloride. The method was successfully applied for the simultaneous determination of the studied drugs in pharmaceutical formulation, with mean percent recoveries for Fexofenadine hydrochloride and pseudoephedrine hydrochloride of 99.49 ± 0.931 and 98.67 ± 0.634, respectively, and in spiked human plasma, with mean percent recoveries for Fexofenadine hydrochloride and pseudoephedrine hydrochloride of 95.21 ± 1.938 and 94.89 ± 1.763, respectively. Furthermore, the greenness of the described method was assessed using four different tools namely, the national environmental method index, the analytical eco-scale, the green analytical procedure index and the AGREE evaluation method. The proposed method seemed to be superior to the reported HPLC method with respect to the metrics of the greenness characters.
PubMed: 35986381
DOI: 10.1186/s13065-022-00855-5 -
Journal of AOAC International Sep 2022Common cold and cough preparations represent a huge segment of the global pharmaceutical market. Recently, cold/cough formulations containing paracetamol (PAR) have... (Review)
Review
Novel Spectrophotometric Approaches for the Simultaneous Quantification of Ternary Common Cold Mixture Containing Paracetamol with a Challenging Formulation Ratio: Greenness Profile Evaluation.
BACKGROUND
Common cold and cough preparations represent a huge segment of the global pharmaceutical market. Recently, cold/cough formulations containing paracetamol (PAR) have attracted significant attention as PAR has been implemented into the supportive treatment of mild cases of COVID-19 as the first-line antipyretic. From a literature review, no method has been reported yet for simultaneous estimation of PAR, pseudoephedrine hydrochloride (PSE) and carbinoxamine maleate (CRX) in any matrix. Thus, there is an urgent need for smart and green methods that would enable quantification of the cited components in their challenging ratio.
OBJECTIVES
The aim of this work is to develop and validate the first UV spectrophotometric methods for simultaneous determination of the selected drugs taking into consideration the list of challenges including the highly overlapping features and spectral interferences in the cited mixture.
METHODS
Namely, the proposed methods are: direct spectrophotometry, dual wavelength, first derivative, derivative ratio, ratio difference, constant center coupled with spectrum subtraction, and the constant multiplication method paired with spectrum subtraction.
RESULTS
These methods were linear over the concentration range of 2.5-35, 1.5-20, and 4.5-35 μg/mL for PAR, PSE and CRX, respectively. These methods fulfill the validity parameters according to International Conference on Harmonization (ICH) guidelines. The results obtained were statistically benchmarked to the official ones where no significant difference was noticed.
CONCLUSION
The developed methods are successfully applied for concurrent quantification of the studied components in the marketed dosage form without interference from matrix excipients. The impact on the environment was assessed by five green metrics, namely a recent Analytical greenness (AGREE) metric algorithm based on the green analytical chemistry framework, Green Analytical Procedure Index (GAPI), Eco-Scale, Assessment of Green Profile (AGP), and National Environmental Methods Index (NEMI).
HIGHLIGHTS
Eco-friendly and successive spectrophotometric methods were firstly developed in this work, for the simultaneous quantification of PAR, PSE and CRX. These approaches incorporate a simple enrichment-aided technique to augment their spectrophotometric signals, facilitating the accurate quantitation of the minor component in the cited mixture.
Topics: Acetaminophen; COVID-19; Common Cold; Cough; Humans; Pseudoephedrine; Spectrophotometry
PubMed: 35916665
DOI: 10.1093/jaoacint/qsac031 -
Dental and Medical Problems 2022Changes in the color of the teeth are a common dental finding associated with clinical and esthetic problems. Especially, the discoloration of primary teeth can cause...
BACKGROUND
Changes in the color of the teeth are a common dental finding associated with clinical and esthetic problems. Especially, the discoloration of primary teeth can cause parental concern and have a negative effect on social interactions between preschool children.
OBJECTIVES
The aim of the study was to evaluate the effect of pediatric drugs and an oral rinse on the discoloration of primary teeth.
MATERIAL AND METHODS
Similar to medication intake recommendations, 7 primary teeth in each group were immersed for 1 min in one of 11 different solutions at 8-hour intervals for 1 week. The color values were obtained using a spectrophotometer (VITA EasyShade®) at baseline and after 1 week. The color change (ΔE*) values were calculated according to the CIELab system. The statistical analysis was conducted using the one-way analysis of variance (ANOVA) and Tukey's post hoc tests at a p-value <0.05.
RESULTS
When comparing values L*, a* and b* at baseline and day 7, a statistically significant difference was found in the a* value for the teeth immersed in pseudoephedrine (p = 0.012). There were also statistically significant differences with regard to color change at day 7 (ΔE*7) between the pseudoephedrine and chlorhexidine as well as pseudoephedrine and control groups (p = 0.034 and p = 0.030, respectively).
CONCLUSIONS
The ΔE*7 value for pseudoephedrine was 3.7 after 1 week, indicating that it may have the potential to cause significant tooth discoloration when used for a long period. Clinicians and children's families should be aware of the fact that some pediatric drugs can cause tooth discoloration.
Topics: Color; Esthetics, Dental; Humans; Mouthwashes; Pseudoephedrine; Tooth Discoloration; Tooth, Deciduous
PubMed: 35703497
DOI: 10.17219/dmp/133406 -
Clinical Pharmacology and Therapeutics Sep 2022Green tea (GT) alters the disposition of a number of drugs, such as nadolol and lisinopril. However, it is unknown whether GT affects disposition of hydrophilic... (Randomized Controlled Trial)
Randomized Controlled Trial
Green tea (GT) alters the disposition of a number of drugs, such as nadolol and lisinopril. However, it is unknown whether GT affects disposition of hydrophilic anti-allergic drugs. The purpose of this study was to investigate whether pharmacokinetics of fexofenadine and pseudoephedrine are affected by catechins, major GT components. A randomized, open, 2-phase crossover study was conducted in 10 healthy Japanese volunteers. After overnight fasting, subjects were simultaneously administered fexofenadine (60 mg) and pseudoephedrine (120 mg) with an aqueous solution of green tea extract (GTE) containing (-)-epigallocatechin gallate (EGCG) of ~ 300 mg or water (control). In vitro transport assays were performed using HEK293 cells stably expressing organic anion transporting polypeptide (OATP)1A2 to evaluate the inhibitory effect of EGCG on OATP1A2-mediated fexofenadine transport. In the GTE phase, the area under the plasma concentration-time curve and the amount excreted unchanged into urine for 24 hours of fexofenadine were significantly decreased by 70% (P < 0.001) and 67% (P < 0.001), respectively, compared with control. There were no differences in time to maximum plasma concentration and the elimination half-life of fexofenadine between phases. Fexofenadine was confirmed to be a substrate of OATP1A2, and EGCG (100 and 1,000 μM) and GTE (0.1 and 1 mg/mL) inhibited OATP1A2-mediated uptake of fexofenadine. On the contrary, the concomitant administration of GTE did not influence the pharmacokinetics of pseudoephedrine. These results suggest that intake of GT may result in a markedly reduced exposure of fexofenadine, but not of pseudoephedrine, putatively by inhibiting OATP1A2-mediated intestinal absorption.
Topics: Antioxidants; Catechin; Cross-Over Studies; HEK293 Cells; Healthy Volunteers; Humans; Pharmaceutical Preparations; Plant Extracts; Pseudoephedrine; Tea; Terfenadine
PubMed: 35678032
DOI: 10.1002/cpt.2682 -
Biomedicine & Pharmacotherapy =... Jun 2022We investigated the protective effects of ephedra herb (HEPH) on adriamycin-induced testicular toxicity in rats and explored the potential mechanisms underlying these...
OBJECTIVE
We investigated the protective effects of ephedra herb (HEPH) on adriamycin-induced testicular toxicity in rats and explored the potential mechanisms underlying these effects.
METHODS
A rat model of adriamycin injury was established, and sperm motility-related indicator and oxidative stress levels in the testis were evaluated. Serum levels of sex hormones and levels of testicular cell apoptosis were detected by enzyme-linked immunosorbent assay and flow cytometry, respectively. Western blotting (WB), immunofluorescence analyses, and reverse transcription-polymerase chain reaction (RT-PCR) were performed to evaluate the gonadotropin-releasing hormone (GnRH) signalling pathway- and meiosis-related genes and proteins. In subsequent in vitro experiments, adriamycin was used to stimulate GC-1 cells, which were treated with HEPH, ephedrine, or pseudoephedrine. Cell viability was assessed using flow cytometry to detect apoptosis and reactive oxygen species, whereas the GnRH signalling pathway and levels of meiosis-related genes and proteins were evaluated by InCell WB, a high-content imaging system, and RT-PCR.
RESULTS
Per in vivo experiments, HEPH restored testicular weight and function, sperm characteristics, serum and tissue hormonal levels, and antioxidant defences and significantly activated the GnRH signalling pathway- and meiosis-related protein levels. All protective effects of HEPH against adriamycin-induced injury were antagonised by the GnRH antagonist cetrorelix. In vitro, HEPH, ephedrine, and pseudoephedrine significantly reduced adriamycin-induced GC-1 cell apoptosis and reactive oxygen species levels and increased the expression of GnRH signalling pathway- and meiosis-related proteins. The effect of pseudoephedrine was greater than that of ephedrine, and these findings may be an important basis for understanding the effects of HEPH.
Topics: Animals; Doxorubicin; Ephedra; Ephedrine; Gonadotropin-Releasing Hormone; Male; Pseudoephedrine; Rats; Reactive Oxygen Species; Sperm Motility; Testis
PubMed: 35658231
DOI: 10.1016/j.biopha.2022.113061 -
Chemistry (Weinheim An Der Bergstrasse,... Jul 2022(1S,2S)-N-methyl-pseudoephedrine (MPS) was used as organic structure-directing agent (OSDA) for the synthesis of Mg-doped nanoporous aluminophosphates. This molecule...
(1S,2S)-N-methyl-pseudoephedrine (MPS) was used as organic structure-directing agent (OSDA) for the synthesis of Mg-doped nanoporous aluminophosphates. This molecule displays a particular conformational behavior, where the presence of H-bond donor and acceptor groups provide a rigid conformational space with one asymmetric conformation preferentially occurring. MPS drives the crystallization of Mg-containing AFI materials. Characterization of these materials shows that the OSDA incorporate as protonated species, arranged as head-to-tail monomers. Combination of three-dimensional electron diffraction with high-resolution synchrotron powder X-ray diffraction allowed to locate both the Mg and the organic species. Interestingly, results showed that the spatial incorporation of Mg is driven by the hydroxyl groups of the organic cation through the development of H-bonds with negatively-charged MgO tetrahedra. This work demonstrates that H-bond forming groups can be used to drive the spatial incorporation of low-valent dopants within zeolitic frameworks, a highly desired aim in order to control their catalytic activity and selectivity.
Topics: Catalytic Domain; Crystallization; Zeolites
PubMed: 35510690
DOI: 10.1002/chem.202200702 -
International Journal of Nanomedicine 2022Pseudoephedrine (PSE) has rapid absorption and metabolism, which limits its pharmacologic actions. We postulated that pseudoephedrine nanoparticles (PSE-NPs) with high...
PURPOSE
Pseudoephedrine (PSE) has rapid absorption and metabolism, which limits its pharmacologic actions. We postulated that pseudoephedrine nanoparticles (PSE-NPs) with high bioavailability could overcome this limitation. The defensive function of PSE-NPs nanoparticles against adriamycin-induced reproductive toxicity in mice was studied.
METHODS
We encapsulated PSE in polylactide-polyglycolide nanoparticles (PLGA-NPs) and verified their protective activity against testicular injury in vivo and in vitro.
RESULTS
We report a promising delivery system that loads PSE into PLGA-NPs and finally assembles it into a nanocomposite particle. In vitro, PSE-NPs reduced the adriamycin-induced apoptosis of GC-1 cells significantly, improved mitochondrial energy metabolism and promoted expression of the proteins related to the gonadotropin-releasing hormone (GnRh) receptor signaling pathway. In vivo, evaluation of sperm indices and histology showed that adriamycin could induce testicular toxicity. PSE-NPs significantly increased the sperm motility of mice, reduced the percent apoptosis and oxidative stress of testes, increased serum levels of GnRh, activated the GnRhR signaling pathway in testes and promoted expression of meiosis-related factors.
CONCLUSION
In view of their safety and efficiency, these PSE-NPs have potential applications in alleviating adriamycin-induced reproductive toxicity.
Topics: Animals; Doxorubicin; Gonadotropin-Releasing Hormone; Male; Mice; Nanoparticles; Pseudoephedrine; Signal Transduction; Sperm Motility
PubMed: 35401001
DOI: 10.2147/IJN.S348673