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Scientific Reports Aug 2023Orphenadrine (ORP), dimenhydrinate (DMN), and cinnarizine (CNN) were investigated using green-sensitive spectrofluorometric methods. Method, I used for determination of...
Orphenadrine (ORP), dimenhydrinate (DMN), and cinnarizine (CNN) were investigated using green-sensitive spectrofluorometric methods. Method, I used for determination of DMN in 0.1 M hydrochloric acid (HCl) and 1.0% sodium dodecyl sulphate (SDS) at 286 nm after λ 222 nm, while for determination of ORP in 1.0% w/v SDS involves measuring the fluorescence at 285 nm after λ 220 nm. For DMN and ORP, the detection and quantitation limits were 2.99 and 4.71 and 9.08 and 14.29 ng/mL, respectively. The ranges of DMN and ORP were 0.10-1.0 and 0.04-0.5 µg/mL, respectively, in micellar aqueous solution. Method II, the derivative intensities of DMN and CNN were measured at a fixed of different wavelength between the excitation and the emission wavelengths (Δλ) = 60 nm at 282 and 322 nm, at the zero crossing of each other, respectively. The detection and quantitation limits for DMN and CNN were 1.77 and 0.88 ng/mL and 5.36 and 2.65 ng/mL, correspondingly, through the entire range of 0.1-1.0 µg/mL for DMN and CNN. The linearity was perfectly determined through the higher values of the correlation coefficient ranging from 0.9997 to 0.9999 for both direct and synchronous methods. The precision of the proposed methods was also confirmed via the lower values of the standard deviation which ranged from 0.39 to 1.11. The technique was expanded to analyze this mixture in combined tablets and laboratory-prepared mixtures. The method validation was done depending on the international conference on harmonization (ICH) recommendations. An analysis of the statistical data revealed a high agreement between the proposed data and the comparison methodology. Three different assessment methods demonstrated the greenness of the technique.
Topics: Cinnarizine; Dimenhydrinate; Hydrochloric Acid; Laboratories; Orphenadrine; Spectrometry, Fluorescence
PubMed: 37599333
DOI: 10.1038/s41598-023-40559-x -
Environmental Science and Pollution... Mar 2024The uptake, translocation, and metabolization of four widely used drugs, amitriptyline, orphenadrine, lidocaine, and tramadol, were investigated in a laboratory study....
The uptake, translocation, and metabolization of four widely used drugs, amitriptyline, orphenadrine, lidocaine, and tramadol, were investigated in a laboratory study. Cress (Lepidium sativum L.) and pea (Pisum sativum L.) were employed as model plants. These plants were grown in tap water containing the selected pharmaceuticals at concentrations ranging from 0.010 to 10 mg L, whereby the latter concentration was employed for the (tentative) identification of drug-related metabolites formed within the plant. Thereby, mainly phase I metabolites were detected. Time-resolved uptake studies, with sampling after 1, 2, 4, 8, and 16 days, revealed that all four pharmaceuticals were taken up by the roots and further relocated to plant stem and leaves. Also in these studies, the corresponding phase I metabolites could be detected, and their translocation from root to stem (pea only) and finally leaves could be investigated.
Topics: Amitriptyline; Pisum sativum; Brassicaceae; Orphenadrine; Tramadol; Lidocaine; Plants; Vegetables; Pharmaceutical Preparations; Plant Roots
PubMed: 38363510
DOI: 10.1007/s11356-024-32379-x -
Journal of Pain Research 2024Skeletal muscle relaxants (SMRs) are widely used in treating musculoskeletal conditions. All SMRs, with the exception of baclofen and tizanidine, are on the list of 2023... (Review)
Review
BACKGROUND
Skeletal muscle relaxants (SMRs) are widely used in treating musculoskeletal conditions. All SMRs, with the exception of baclofen and tizanidine, are on the list of 2023 American Geriatrics Society Beers Criteria for potentially inappropriate medication use in older adults. In our geriatric practice, off-label use of tizanidine as preemptive analgesia drove us to find recent advances in its pharmacology and therapeutics. An update review of tizanidine was thus presented, aiming to bring the latest knowledge to clinicians and promote further research and practical exploration.
METHODS
Relevant literature up to December 2023 was identified through searches of PubMed, Web of Science, and Embase.
RESULTS
Tizanidine, a centrally acting alpha-2 adrenoceptor agonist with both antispastic and antispasmodic activity, shows efficacy in the common indications for all SMRs. From the perspective of drug safety, tizanidine has lower incidences of adverse events (injury, delirium, encephalopathy, falls, and opioid overdose) compared to baclofen, no association with risk of Alzheimer's disease as with orphenadrine, no risk of serotonin syndrome like metaxalone when comedicated with serotonergic drugs, no significant pharmacokinetic changes in CYP2C19 poor metabolizers unlike diazepam and carisoprodol, and no physically addictive or abuse properties like carisoprodol and diazepam. From the perspective of new and potential therapeutic uses, tizanidine has additional benefits (eg, gastroprotection that can improve patient tolerance to nonsteroidal anti-inflammatory agents, anti-neuropathic pain, a key component of multimodal analgesia strategy to reduce early postoperative pain, and anti-tumor effects). New delivery systems of tizanidine are developing to improve the pharmacokinetics of oral products, including buccal patches, transdermal delivery systems, nasal spray, and in situ rectal gel.
CONCLUSION
Tizanidine is an SMR with unique features and may be an optimal initial choice for older adults. There would be more scientific studies, wider therapeutic applications, and new drug formulations in the future.
PubMed: 38529017
DOI: 10.2147/JPR.S461032 -
Scientific Reports May 2024An experimental design and response surface methodologies using Plackett-Burman and Box-Behnken designs were applied for selecting and optimizing the most appropriate...
An experimental design and response surface methodologies using Plackett-Burman and Box-Behnken designs were applied for selecting and optimizing the most appropriate parameters which significantly affect the separation and quantitative estimation of five skeletal muscle relaxants and four analgesic drugs (baclofen, methocarbamol, dantrolene sodium, orphenadrine citrate, cyclobenzaprine hydrochloride, ketoprofen, etoricoxib, ibuprofen, and mefenamic acid) with a relatively short duration of analysis in a single run. For the separation of the nine drugs, an INERTSIL ODS-V3-5 µm C18 column (250 × 4.6 mm I.D.) was used with the optimum mobile phase conditions (45.15 mM ammonium acetate buffer pH 5.56 adjusted with acetic acid, acetonitrile, and methanol in a ratio of 30.5:29.5:40, v/v/v with a flow rate of 1.5 mL/min) and UV-detection at 220 nm. The optimized method was successfully subjected to the validation steps as described in ICH guidelines for linearity, precision, accuracy, robustness, and sensitivity. The optimized and validated method was effectively applied to determine the content of the studied drugs in their pharmaceutical preparations and to expand its applicability to the counterfeit estimation of etoricoxib in different brands of tablet dosage forms.
Topics: Chromatography, High Pressure Liquid; Analgesics; Neuromuscular Agents; Reproducibility of Results; Chromatography, Reverse-Phase; Research Design
PubMed: 38710733
DOI: 10.1038/s41598-024-58381-4 -
International Journal of Molecular... Mar 2024Cisplatin (CDDP) stands out as an effective chemotherapeutic agent; however, its application is linked to the development of significant adverse effects, notably nephro-...
Cisplatin (CDDP) stands out as an effective chemotherapeutic agent; however, its application is linked to the development of significant adverse effects, notably nephro- and ototoxicity. The human organic cation transporter 2 (hOCT2), found in abundance in the basolateral membrane domain of renal proximal tubules and the Corti organ, plays a crucial role in the initiation of nephro- and ototoxicity associated with CDDP by facilitating its uptake in kidney and ear cells. Given its limited presence in cancer cells, hOCT2 emerges as a potential druggable target for mitigating unwanted toxicities associated with CDDP. Potential strategies for mitigating CDDP toxicities include competing with the uptake of CDDP by hOCT2 or inhibiting hOCT2 activity through rapid regulation mediated by specific signaling pathways. This study investigated the interaction between the already approved cationic drugs disopyramide, imipramine, and orphenadrine with hOCT2 that is stably expressed in human embryonic kidney cells. Regarding disopyramide, its influence on CDDP cellular transport by hOCT2 was further characterized through inductively coupled plasma isotope dilution mass spectrometry. Additionally, its potential protective effects against cellular toxicity induced by CDDP were assessed using a cytotoxicity test. Given that hOCT2 is typically expressed in the basolateral membrane of polarized cells, with specific regulatory mechanisms, this work studied the regulation of hOCT2 that is stably expressed in Madin-Darby Canine Kidney (MDCK) cells. These cells were cultured in a matrix to induce the formation of cysts, exposing hOCT2 in the basolateral plasma membrane domain, which was freely accessible to experimental solutions. The study specifically tested the regulation of ASP uptake by hOCT2 in MDCK cysts through the inhibition of casein kinase II (CKII), calmodulin, or p56 tyrosine kinase. Furthermore, the impact of this manipulation on the cellular toxicity induced by CDDP was examined using a cytotoxicity test. All three drugs-disopyramide, imipramine, and orphenadrine-demonstrated inhibition of ASP uptake, with IC values in the micromolar (µM) range. Notably, disopyramide produced a significant reduction in the CDDP cellular toxicity and platinum cellular accumulation when co-incubated with CDDP. The activity of hOCT2 in MDCK cysts experienced a significant down-regulation under inhibition of CKII, calmodulin, or p56 tyrosine kinase. Interestingly, only the inhibition of p56 tyrosine kinase demonstrated the capability to protect the cells against CDDP toxicity. In conclusion, certain interventions targeting hOCT2 have demonstrated the ability to reduce CDDP cytotoxicity, at least in vitro. Further investigations in in vivo systems are warranted to ascertain their potential applicability as co-treatments for mitigating undesired toxicities associated with CDDP in patients.
Topics: Humans; Animals; Dogs; Organic Cation Transporter 2; Organic Cation Transport Proteins; Cisplatin; Disopyramide; Calmodulin; Imipramine; Orphenadrine; Ototoxicity; Madin Darby Canine Kidney Cells; Protein-Tyrosine Kinases; Cysts
PubMed: 38474165
DOI: 10.3390/ijms25052922 -
RSC Advances Oct 2023Metal organic frameworks (MOFs), with structural tunability, high metal content and large surface area have recently attracted the attention of researchers in the field...
Metal organic frameworks (MOFs), with structural tunability, high metal content and large surface area have recently attracted the attention of researchers in the field of electrochemistry. In this work, an unprecedented use of multi-walled carbon nanotubes (MWCNTs)/copper-based metal-organic framework (Cu-BTC MOF) composite as an ion-to-electron transducer in a potentiometric sensor is proposed for the determination of orphenadrine citrate. A comparative study was conducted between three proposed glassy carbon electrodes, Cu-MOF, (MWCNTs) and MWCNTs/Cu-MOF composite based sensors, where Cu-MOF, MWCNTs and their composite were utilized as the ion-to-electron transducers. The sensors were developed for accurate and precise determination of orphenadrine citrate in pharmaceutical dosage form, spiked real human plasma and artificial cerebrospinal fluid (ACSF). The sensors employed β-cyclodextrin as a recognition element with the aid of potassium tetrakis(4-chlorophenyl)borate (KTpCIPB) as a lipophilic ion exchanger. The sensors that were assessed based on the guidelines recommended by IUPAC and demonstrated a linear response within the concentration range of 10 M to 10 M, 10 M to 10 M and 10 M to 10 M for Cu-MOF, MWCNTs and MWCNTs/Cu-MOF composite based sensors, respectively. MWCNTs/Cu-MOF composite based sensor showed superior performance over other sensors regarding lower limit of detection (LOD), wider linearity range and faster response. The sensors demonstrated their potential as effective options for the analysis of orphenadrine citrate in quality control laboratories and in different healthcare activities.
PubMed: 37876650
DOI: 10.1039/d3ra06710f