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Experimental & Molecular Medicine Apr 2024Sarcopenia, the progressive decline in skeletal muscle mass and function, is observed in various conditions, including cancer and aging. The complex molecular biology of...
Sarcopenia, the progressive decline in skeletal muscle mass and function, is observed in various conditions, including cancer and aging. The complex molecular biology of sarcopenia has posed challenges for the development of FDA-approved medications, which have mainly focused on dietary supplementation. Targeting a single gene may not be sufficient to address the broad range of processes involved in muscle loss. This study analyzed the gene expression signatures associated with cancer formation and 5-FU chemotherapy-induced muscle wasting. Our findings suggest that dimenhydrinate, a combination of 8-chlorotheophylline and diphenhydramine, is a potential therapeutic for sarcopenia. In vitro experiments demonstrated that dimenhydrinate promotes muscle progenitor cell proliferation through the phosphorylation of Nrf2 by 8-chlorotheophylline and promotes myotube formation through diphenhydramine-induced autophagy. Furthermore, in various in vivo sarcopenia models, dimenhydrinate induced rapid muscle tissue regeneration. It improved muscle regeneration in animals with Duchenne muscular dystrophy (DMD) and facilitated muscle and fat recovery in animals with chemotherapy-induced sarcopenia. As an FDA-approved drug, dimenhydrinate could be applied for sarcopenia treatment after a relatively short development period, providing hope for individuals suffering from this debilitating condition.
Topics: Animals; Autophagy; Mice; Transcriptome; Humans; Protein Biosynthesis; Disease Models, Animal; Muscle, Skeletal; Gene Expression Profiling; Sarcopenia; Muscular Dystrophy, Duchenne
PubMed: 38556548
DOI: 10.1038/s12276-024-01189-z -
Acute Inhibition of the Human Kv1.5 Channel by H Receptor Antagonist Dimenhydrinate: Mode of Action.Biological & Pharmaceutical Bulletin 2023Dimenhydrinate, an H receptor antagonist, is generally used for the prevention and treatment of nausea and vomiting. However, cardiac arrhythmias have been reported to...
Dimenhydrinate, an H receptor antagonist, is generally used for the prevention and treatment of nausea and vomiting. However, cardiac arrhythmias have been reported to be associated with the overdose of histamine H receptor antagonists, indicating the probable effect of antihistamines on ion channels. By using a two-microelectrode voltage clamp, we have herein studied the electrophysiological effects of dimenhydrinate on the human Kv1.5 channel in the Xenopus oocyte expression system. Dimenhydrinate acutely and reversibly suppressed the amplitudes of the peak and the steady-state current, within 6 min. The inhibitory effect of dimenhydrinate on the peak and the steady-state Kv1.5 currents increased progressively from -10 to +50 mV. At each test voltage, the drug suppressed both the peak and the steady-state currents to a similar extent. When the oocytes were stimulated at the rates of 5- and 30-s intervals, dimenhydrinate-induced a use-dependent blockade of the human Kv1.5 channel. Dimenhydrinate expedited the timecourse of the Kv1.5 channel activation more effectively than the timecourse of its inactivation. However, the activation and inactivation curves of the channel were not altered by the H receptor antagonist. In conclusion, we found that dimenhydrinate inhibits the human Kv1.5 channel by changing the channel's activation mode, thereby possibly increasing the possibility of triggering cardiac arrhythmias and affecting atrial fibrillation.
Topics: Humans; Dimenhydrinate; Electrophysiological Phenomena; Histamine H1 Antagonists; Oocytes; Potassium Channel Blockers
PubMed: 37779040
DOI: 10.1248/bpb.b23-00170 -
Frontiers in Pharmacology 2023Acquired QT interval prolongations due to drug side effects can result in detrimental arrhythmia. Maternal use of placenta-permeable drugs may lead to fetal exposure,...
Acquired QT interval prolongations due to drug side effects can result in detrimental arrhythmia. Maternal use of placenta-permeable drugs may lead to fetal exposure, thus leading to an increased risk of neonatal QT prolongation and arrhythmia. This study aimed to evaluate the influence of maternal QT-prolonging medication on the neonatal QT interval. In the prospective KUNO-Kids health study, an ongoing population-based birth cohort, we classified maternal medications according to the known risk of QT interval prolongation. Effects on the neonatal QT interval were tested by linear regression analyses, correcting for perinatal confounders (birth weight, gestational age, birth mode, and age at ECG recording). Subgroup analyses were performed for selective serotonin reuptake inhibitors, proton pump inhibitors, and antihistamine dimenhydrinate. Logistic regression analysis was performed using a QTc of 450 ms as the cut-off value. A total of 2,550 pregnant women received a total of 3,990 medications, of which 315 were known to increase the risk of QT prolongation, resulting in 105 (4.1%) neonates exposed in the last month of pregnancy. Overall, the mean age of the neonates at ECG was 1.9 days and the mean QTc (Bazett) was 414 ms. Univariate (regression coefficient -2.62, = 0.288) and multivariate (regression coefficient -3.55, = 0.146) regression analyses showed no significant effect of fetal medication exposure on the neonatal QT interval, neither in the overall nor in the subgroup analysis. Logistic regression analysis showed no association of exposure to maternal medication with an increased risk of neonatal QT interval prolongation (OR (odds ratio) 0.34, = 0.14). The currently used maternal medication results in a relevant number of fetuses exposed to QT interval-prolonging drugs. In our cohort, exposure was found to have no effect on the neonatal QT interval.
PubMed: 37608894
DOI: 10.3389/fphar.2023.1193317 -
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 -
Identify travel and health factors influencing well-being of the older adults-a case study in China.Frontiers in Public Health 2023With the increase in aging populations worldwide, the travel well-being of the elders has gained attention. The objective of this study is to examine the nonlinear...
OBJECTIVE
With the increase in aging populations worldwide, the travel well-being of the elders has gained attention. The objective of this study is to examine the nonlinear relationships between the well-being of the older people in China and factors associated with travel and health.
METHOD
Based on the data collected in China, combined embedded feature selection and decision tree built by Gini index were utilized to screen for influential factors and to determine the importance of the features selected. Tamhane's T2 was used to study the differences in the important factors among older people with different levels of travel well-being.
RESULTS
This study found that the travel well-being of older adults depends mainly on accessibility to public places, such as schools and medical facilities, and the availability of bus services. Out of expectation, the most important influential factor of travel well-being of older people is the distance from home to high school. This is related to the traditional Chinese concept of education. In addition, it was found that the body mass index is more important than self-perceived health as an influence factor of travel well-being of the elders in China. Social skills are important factors too.
CONCLUSION
This study investigated various health-related and travel-related factors and their impacts on the travel well-being of older adults Chinese with the overall goal to improve the quality of life of the elders in China. The findings may provide a theoretical basis for the implementation of various transportation management and urban planning and design -related policies to improve the travel well-being of older adults in China.
Topics: Humans; Aged; Travel; Quality of Life; Dimenhydrinate; Travel-Related Illness; Transportation
PubMed: 37538271
DOI: 10.3389/fpubh.2023.1213499 -
Indian Journal of Otolaryngology and... Apr 2023Aim: The aim of the study is to compare the effects of vestibular rehabilitation and pharmacological treatment in benign paroxysmal positional vertigo (BPPV). Materials...
UNLABELLED
Aim: The aim of the study is to compare the effects of vestibular rehabilitation and pharmacological treatment in benign paroxysmal positional vertigo (BPPV). Materials and methods: Thirty patients (40.93 ± 8.66 years old) diagnosed with BPPV were recruited. Patients were equally divided into pharmacological control group and vestibular rehabilitation group. The pharmacological control group was further divided into Group A (n = 8, 2 doses/day, 24 mg betahistine) and Group B (n = 7, 1 dose/day, 50 mg dimenhydrinate in addition to betahistine). Patients in the rehabilitation group underwent repeated head and eye movements, and Epley or Barbecue Roll Maneuvers were applied for 4 weeks. Subjective assessment of vertigo was measured with the visual analog scale. Static balance parameters were measured with the tandem, one-legged stance, and Romberg tests. Dynamic visual acuity was measured with a Snellen chart, and vestibular dysfunction was measured with the Unterberger (Fukuda stepping) test. All parameters were evaluated before and after treatment. Results: Vestibular rehabilitation resulted in greater improvement in severity of vertigo, balance parameters except Romberg test, and vestibular dysfunction than pharmacological therapy (p < 0,001). There was no significant difference in dynamic visual acuity between groups (p = 0,24). The effects of medication with the active ingredients betahistine and dimenhydrinate were similar (p > 0,05). Conclusion: The vestibular rehabilitation method can positively change the severity of vertigo, balance ability, and vestibular dysfunction compared to pharmacological therapy. Dimenhydrinate administered in combination with betahistine was not superior to betahistine alone but can be recommended for its antiemetic effect.
SUPPLEMENTARY INFORMATION
The online version contains supplementary material available at 10.1007/s12070-023-03598-4.
PubMed: 37206852
DOI: 10.1007/s12070-023-03598-4 -
Journal of Family Medicine and Primary... Mar 2023The antihistamine dimenhydrinate as the trigger of acute urinary retention has not been reported. A 35-year-old female with a long-term history of depression treated...
The antihistamine dimenhydrinate as the trigger of acute urinary retention has not been reported. A 35-year-old female with a long-term history of depression treated with sertraline (150 mg/d) since years developed acute urinary retention after having received 100 mg dimenhydrinate intravenously for excessive, postural vertigo. Urinary retention required placement of a disposable catheter, which halted 1.6 liter of urine. Since urinary retention persisted, she received a permanent catheter, which initially halted another 1.2 liter of urine. Urinary retention resolved spontaneously within 48 hours, and the patient was discharged with her previous medication. This case shows that intravenous dimenhydrinate can trigger the development of acute urinary retention in patients under long-term treatment with sertraline, which is why it should be given with caution in this group of patients.
PubMed: 37122660
DOI: 10.4103/jfmpc.jfmpc_1338_22 -
Frontiers in Pharmacology 2023Self-medication is a part of the self-care practices carried out by the elderly in their environment. The aim of this case report is to show how the self-medication of...
Self-medication is a part of the self-care practices carried out by the elderly in their environment. The aim of this case report is to show how the self-medication of fluoxetine and dimenhydrinate in an older adult can induce serotoninergic and cholinergic syndromes, showing symptoms such as nausea, tachycardia, tremor, loss of appetite, memory loss, decreased vision, falls, and increased urination. An older adult who has been diagnosed with arterial hypertension, dyslipidemia, diabetes mellitus, and a recent diagnosis of essential thrombosis is the subject of this case report. After the analysis of the case, cessation of fluoxetine was recommended to avoid withdrawal symptoms, therefore decreasing the need for dimenhydrinate and the medicines used for dyspepsia. After the recommendation, the patient showed an improvement in the symptoms. Finally, the comprehensive evaluation process of the medication in the Medicines Optimization Unit achieved the detection of the problem and improved the patient's health condition.
PubMed: 36874029
DOI: 10.3389/fphar.2023.1080249 -
The Cochrane Database of Systematic... Oct 2022Motion sickness is a syndrome that occurs as a result of passive body movement in response to actual motion, or the illusion of motion when exposed to virtual and moving... (Review)
Review
BACKGROUND
Motion sickness is a syndrome that occurs as a result of passive body movement in response to actual motion, or the illusion of motion when exposed to virtual and moving visual environments. The most common symptoms are nausea and vomiting. Antihistamines have been used in the management of motion sickness for decades, however studies have shown conflicting results regarding their efficacy.
OBJECTIVES
To assess the effectiveness of antihistamines in the prevention and treatment of motion sickness in adults and children.
SEARCH METHODS
The Cochrane ENT Information Specialist searched the Cochrane ENT Register; Central Register of Controlled Trials; Ovid MEDLINE; Ovid Embase; Web of Science; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished trials. The date of the search was 7 December 2021.
SELECTION CRITERIA
Randomised controlled trials (RCTs) in susceptible adults and children in whom motion sickness was induced under natural conditions such as air, sea and land transportation. We also included studies in which motion sickness was induced under experimental conditions (analysed separately). Antihistamines were included regardless of class, route or dosage and compared to no treatment, placebo or any other pharmacological or non-pharmacological interventions.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methods. Our primary outcomes were 1) the proportion of susceptible participants who did not experience any motion sickness symptoms; 2) the proportion of susceptible participants who experienced a reduction or resolution of existing symptoms. Secondary outcomes were 1) physiological measures (heart rate, core temperature and gastric tachyarrhythmia (electrogastrography)) and 2) adverse effects (sedation, impaired cognition, blurred vision). We used GRADE to assess the certainty of the evidence for each outcome.
MAIN RESULTS
We included nine RCTs (658 participants). Studies were conducted across seven countries, with an overall age range of 16 to 55 years. Motion sickness was induced naturally in six studies and experimentally in four studies (rotating chair). All the naturally induced studies only evaluated first-generation antihistamines (cinnarizine and dimenhydrinate). Risk of bias across the studies varied, with mostly low risk for random sequence generation and allocation concealment, and mostly high risk for selective reporting. Only the experimentally induced studies measured physiological parameters and only the naturally induced studies evaluated adverse effects. There were no studies that clearly assessed the paediatric population. Antihistamines versus placebo or no treatment Antihistamines are probably more effective than placebo at preventing motion sickness symptoms under natural conditions (symptoms prevented: 25% placebo; 40% antihistamines) (risk ratio (RR) 1.81, 95% confidence interval (CI) 1.23 to 2.66; 3 studies; 240 participants) (moderate-certainty). The evidence is very uncertain about the effect of antihistamines on preventing motion sickness under experimental conditions (standardised mean difference (SMD) 0.32, 95% CI -0.18 to 0.83; 2 studies; 62 participants) (very low-certainty). No studies reported results on the resolution of existing motion sickness symptoms. Antihistamines may result in little or no difference in gastric tachyarrhythmia under experimental conditions (mean difference (MD) -2.2, 95% CI -11.71 to 7.31; 1 study; 42 participants) (low-certainty). No studies reported results for any other physiological measures. When compared to placebo, antihistamines may be more likely to cause sedation (sedation: 44% placebo; 66% antihistamines) (RR 1.51, 95% CI 1.12 to 2.02; 2 studies; 190 participants) (low-certainty); they may result in little or no difference in blurred vision (blurred vision: 12.5% placebo; 14% antihistamines) (RR 1.14, 95% CI 0.53 to 2.48; 2 studies; 190 participants) (low-certainty); and they may result in little or no difference in terms of impaired cognition (impaired cognition: 33% placebo; 29% antihistamines) (RR 0.89, 95% CI 0.58 to 1.38; 2 studies; 190 participants) (low-certainty). Antihistamines versus scopolamine The evidence is very uncertain about the effect of antihistamines on preventing motion sickness under natural conditions when compared to scopolamine (symptoms prevented: 81% scopolamine; 71% antihistamines) (RR 0.89, 95% CI 0.68 to 1.16; 2 studies; 71 participants) (very low-certainty). No studies were performed under experimental conditions. No studies reported results on the resolution of existing motion sickness symptoms. The evidence is very uncertain about the effect of antihistamines on heart rate under natural conditions (narrative report, 1 study; 20 participants; "No difference in pulse frequency"; very low-certainty). No studies reported results for any other physiological measures. When compared to scopolamine, the evidence is very uncertain about the effect of antihistamines on sedation (sedation: 21% scopolamine; 30% antihistamines) (RR 0.82, 95% CI 0.07 to 9.25; 2 studies; 90 participants) (very low-certainty) and on blurred vision (narrative report: not a significant difference; 1 study; 51 participants; very low-certainty). No studies evaluated impaired cognition. Antihistamines versus antiemetics Antihistamines may result in little or no difference in the prevention of motion sickness under experimental conditions (MD -0.20, 95% CI -10.91 to 10.51; 1 study; 42 participants) (low-certainty). The evidence is of low certainty due to imprecision as the sample size is small and the confidence interval crosses the line of no effect. No studies assessed the effects of antihistamines versus antiemetics under natural conditions. No studies reported results on the resolution of existing motion sickness symptoms. Antihistamines may result in little or no difference in gastric tachyarrhythmia (MD 4.56, 95% CI -3.49 to 12.61; 1 study; 42 participants) (low-certainty). No studies reported results for any other physiological measures. No studies evaluated sedation, impaired cognition or blurred vision. One study reported physiological data for this outcome, evaluating gastric tachyarrhythmia specifically. Antihistamines may result in little or no difference in gastric tachyarrhythmia (MD 4.56, 95% CI -3.49 to 12.61; 1 study; 42 participants; low-certainty evidence). This evidence is of low certainty due to imprecision as the sample size is small and the confidence interval crosses the line of no effect. Antihistamines versus acupuncture The evidence is very uncertain about the effects of antihistamines on the prevention of motion sickness under experimental conditions when compared to acupuncture (RR 1.32, 95% CI 1.12 to 1.57; 1 study; 100 participants) (very low-certainty). This study did not assess the prevention of motion sickness under natural conditions, nor the resolution of existing motion sickness symptoms. There was no study performed under natural conditions. Physiological measures and adverse effects were not reported.
AUTHORS' CONCLUSIONS
There is probably a reduction in the risk of developing motion sickness symptoms under naturally occurring conditions of motion when using first-generation antihistamines, in motion sickness-susceptible adults, compared to placebo. Antihistamines may be more likely to cause sedation when compared to placebo. No studies evaluated the treatment of existing motion sickness, and there are few data on the effect of antihistamines in children. The evidence for all other outcomes and comparisons (versus scopolamine, antiemetics and acupuncture) was of low or very low certainty and we are therefore uncertain about these effects of antihistamines.
Topics: Adolescent; Adult; Antiemetics; Child; Cinnarizine; Dimenhydrinate; Histamine Antagonists; Humans; Middle Aged; Motion Sickness; Scopolamine Derivatives; Young Adult
PubMed: 36250781
DOI: 10.1002/14651858.CD012715.pub2