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Neurochemical Research Feb 2020Motion sickness (MS) is the visceral discomfort caused due to contradicting visual and vestibular inputs to the brain leading to nausea and vomiting. Sensory conflict...
Motion sickness (MS) is the visceral discomfort caused due to contradicting visual and vestibular inputs to the brain leading to nausea and vomiting. Sensory conflict theory which proves histamine elevations as the primary reason for MS provides a path for an effective pharmaco-therapy. We aimed to evaluate the anti-MS effect of hesperidin (HSP) by modulating histamine and histamine receptor H1 (HRH1) expression. The inhibitory effect of HSP on histamine release was studied in KU812 cells treated with 10 µM calcium ionophore. The in vivo anti-MS effect of HSP was evaluated in Balb/c mice. Thirty six mice were divided into six groups namely, normal control (NC, no rotation), hesperidin at 80 mg/kg body weight control (HSP80, no rotation), motion sickness (MS, rotation induced), dimenhydrinate (Standard drug) at 20 mg/kg body weight + rotation (STD + MS), hesperidin at 40 mg/kg body weight + rotation (HSP40 + MS) and hesperidin at 80 mg/kg body weight + rotation (HSP80 + MS). Hypothalamus and brainstem samples were analysed for histamine levels and HRH1 expression by RT-PCR, Western blot and immunohistochemistry analysis. Calcium ionophore treated KU812 cells significantly increased histamine release when compared to control cells. Pre-treatment with HSP inhibited histamine, HRH1 mRNA and protein expression. Histamine, HRH1 mRNA and protein expression in hypothalamus and brainstem samples of MS group increased significantly when compared to the NC group. Pre-treatment with HSP significantly reduced histamine, HRH1 mRNA and protein expression. Thus, indicating that HSP has a potent anti- MS effect by decreasing the elevated levels of histamine, HRH1 mRNA and protein expression in hypothalamus and brainstem regions.
Topics: Animals; Cell Line, Tumor; Female; Hesperidin; Histamine; Humans; Hypothalamus; Mice, Inbred BALB C; Motion Sickness; RNA, Messenger; Receptors, Histamine H1
PubMed: 31782104
DOI: 10.1007/s11064-019-02923-0 -
International Journal of Clinical... Apr 2020Background Despite growing interest in the negative clinical outcomes of multiple anticholinergic use, limited studies have evaluated anticholinergic burden in the...
Background Despite growing interest in the negative clinical outcomes of multiple anticholinergic use, limited studies have evaluated anticholinergic burden in the geriatric population nationally. Objective To evaluate the prevalence of high anticholinergic burden using the newly developed Korean Anticholinergic Burden Scale in comparison with previous tools and to identify associated factors. Setting National insurance data from a cross section (20%) of older Koreans (2016). Methods Anticholinergic burden was measured using the Korean scale in comparison to the Anticholinergic Drug Scale, Anticholinergic Cognitive Burden, and Anticholinergic Risk Scale. High anticholinergic burden was defined as a summed score of ≥ 3 for concurrent medications or a dose-standardized average daily score of ≥ 3, using each anticholinergic scale. Main outcomes measured Prevalence and predictors of high anticholinergic burden. Results Data of 1,292,323 patients were analyzed. According to the Korean scale, the prevalence of high anticholinergic burden was 25.5%. This result was similar to that from the Anticholinergic Drug Scale (24.9%) and Anticholinergic Cognitive Burden (22.2%). Factors associated with an increased likelihood of anticholinergic burden include: age, gender (female), high Charlson comorbidity index score, polypharmacy, medical aid beneficiary, co-morbidities (such as schizophrenia, depression, urinary incontinence, and Parkinson's disease), frequent healthcare visits, various healthcare facilities utilized, and predominantly visiting hospital-level facilities. According to the Korean Anticholinergic Burden Scale, the major drugs contributing to the anticholinergic burden were ranitidine, chlorpheniramine, tramadol, and dimenhydrinate. Conclusion This study showed that 1 in 4 older Koreans are exposed to high anticholinergic burden. The predictors identified in this research might assist pharmacists in early interventions for their patients.
Topics: Age Factors; Aged; Aged, 80 and over; Cholinergic Antagonists; Comorbidity; Dose-Response Relationship, Drug; Drug Therapy, Combination; Drug Utilization; Female; Humans; Insurance Claim Review; Male; Polypharmacy; Republic of Korea; Risk Factors; Sex Factors; Socioeconomic Factors
PubMed: 32281075
DOI: 10.1007/s11096-020-01010-7 -
Scientific Reports Aug 2017The aim of the current manuscript was to test the applicability of a nanocomposite system of penetration enhancer vesicles (PEVs) within polymeric in situ forming gel...
Intranasally administered in situ gelling nanocomposite system of dimenhydrinate: preparation, characterization and pharmacodynamic applicability in chemotherapy induced emesis model.
The aim of the current manuscript was to test the applicability of a nanocomposite system of penetration enhancer vesicles (PEVs) within polymeric in situ forming gel network composed of poloxamer and hyaluronic acid for the intranasal delivery of the antiemetic dimenhydrinate (DMH). PEVs were prepared using phospholipids and labrasol/transcutol/PEG 400 as penetration enhancers, and characterized for entrapment efficiency (EE%), particle size, zeta potential and morphology. The nanocomposite in situ forming gel system was characterized for its sol-gel temperature, viscosity and mucoadhesiveness, and was pharmacodynamically tested on a cisplatin induced emesis model in rats in terms of food, water, kaolin intake and stomach weight content. The selected PEVs formula displayed EE% of 83% for DMH, particle size of 121 nm and a surface charge of 0.83 mV. The selected nanocomposite in situ gelling formula showed a viscosity of 2.13 Pa.S, mucoadhesive force of 0.62 N and DMH controlled release over 6 hours. The pharmacodynamic study showed the superiority of the nanocomposite in situ gelling formula; being administered at a lower dose than the oral marketed formula. The described nanocomposite system proved to be successful for the intranasal delivery of DMH, thus presenting a promising delivery modality for similar antiemetics.
Topics: Administration, Intranasal; Animals; Antiemetics; Cisplatin; Dimenhydrinate; Drinking; Drug Compounding; Eating; Gels; Male; Microscopy, Electron, Transmission; Molecular Structure; Nanocomposites; Rats, Wistar; Viscosity; Vomiting
PubMed: 28855590
DOI: 10.1038/s41598-017-10032-7 -
Clinical Hemorheology and... 2018In weightlessness, alterations in organ systems have been reported. The microcirculation consists of a network of blood vessels with diameters of a few μm. It is...
BACKGROUND
In weightlessness, alterations in organ systems have been reported. The microcirculation consists of a network of blood vessels with diameters of a few μm. It is considered the largest part of the circulatory system of the human body and essential for exchange of gas, nutrients and waste products. An investigation of the microcirculation in weightlessness seems warranted but has not yet been performed.
OBJECTIVE
In this paper, we outline a study in which we will investigate the possible interrelations between weightlessness and microcirculation. We will induce weightlessness in the course of parabolic flight maneuvers, which will be conducted during a parabolic flight campaign. In this study protocol also an evaluation of a possible influence of parabolic flight premedication on microcirculation will be described.
METHODS
The microcirculation will be investigated by sublingual intravital measurements applying sidestream darkfield microscopy. Parameters of macrocirculation such as heart rate, blood pressure and blood oxygenation will also be investigated.
RESULTS
In our pre-study experiments, neither dimenhydrinate nor scopolamine altered microcirculation.
CONCLUSIONS
As the application of motion sickness therapy did not alter microcirculation, it will be applied during the parabolic flight maneuvers of the campaign. Our results might deepen the understanding of microcirculation on space missions and on earth.
Topics: Humans; Intravital Microscopy; Microcirculation; Weightlessness
PubMed: 29710687
DOI: 10.3233/CH-170366 -
Pediatric Neurology Mar 2016Paroxysmal movement disorders including paroxysmal tonic upward gaze of infancy and paroxysmal dystonia of infancy are benign but uncommon movement disorders seen in...
BACKGROUND
Paroxysmal movement disorders including paroxysmal tonic upward gaze of infancy and paroxysmal dystonia of infancy are benign but uncommon movement disorders seen in young children. Although symptoms are intermittent and resolve spontaneously, they can cause discomfort and distress for the child. Current treatment options are limited to dopaminergic agents or anticonvulsants with limited efficacy.
PATIENT DESCRIPTION
The authors present a child with paroxysmal tonic upward gaze of infancy and another with paroxysmal dystonia of infancy, both of whom responded successfully to treatment with low-dose dimenhydrinate or diphenhydramine, respectively.
DISCUSSION
Dimenhydrinate and diphenhydramine both exert anticholinergic activity and have limited toxicity at low doses. This property makes either compound an attractive therapeutic option for paroxysmal movement disorders in infancy. These agents are generally well tolerated.
Topics: Dimenhydrinate; Diphenhydramine; Electroencephalography; Histamine H1 Antagonists; Humans; Infant; Male; Movement Disorders
PubMed: 26726052
DOI: 10.1016/j.pediatrneurol.2015.10.019 -
Spectrochimica Acta. Part A, Molecular... 2015Simultaneous determination of Dimenhydrinate (DIM) and Cinnarizine (CIN) binary mixture with simple procedures were applied. Three ratio manipulating spectrophotometric...
Simultaneous determination of Dimenhydrinate (DIM) and Cinnarizine (CIN) binary mixture with simple procedures were applied. Three ratio manipulating spectrophotometric methods were proposed. Normalized spectrum was utilized as a divisor for simultaneous determination of both drugs with minimum manipulation steps. The proposed methods were simultaneous constant center (SCC), simultaneous derivative ratio spectrophotometry (S(1)DD) and ratio H-point standard addition method (RHPSAM). Peak amplitudes at isoabsorptive point in ratio spectra were measured for determination of total concentrations of DIM and CIN. For subsequent determination of DIM concentration, difference between peak amplitudes at 250 nm and 267 nm were used in SCC. While the peak amplitude at 275 nm of the first derivative ratio spectra were used in S(1)DD; then subtraction of DIM concentration from the total one provided the CIN concentration. The last RHPSAM was a dual wavelength method in which two calibrations were plotted at 220 nm and 230 nm. The coordinates of intersection point between the two calibration lines were corresponding to DIM and CIN concentrations. The proposed methods were successfully applied for combined dosage form analysis, Moreover statistical comparison between the proposed and reported spectrophotometric methods was applied.
Topics: Antiemetics; Cinnarizine; Dimenhydrinate; Dosage Forms; Drug Combinations; Histamine H1 Antagonists; Spectrophotometry
PubMed: 26037499
DOI: 10.1016/j.saa.2015.05.048 -
The Laryngoscope Oct 2014To investigate the characteristics of residual symptoms and to evaluate the effects of adjuvant vestibular suppressants on residual symptoms after successful canalith... (Comparative Study)
Comparative Study Randomized Controlled Trial
OBJECTIVES/HYPOTHESIS
To investigate the characteristics of residual symptoms and to evaluate the effects of adjuvant vestibular suppressants on residual symptoms after successful canalith repositioning procedures (CRPs).
STUDY DESIGN
Individual randomized controlled trial.
METHODS
One hundred fifty patients with idiopathic benign paroxysmal positional vertigo who achieved successful CRPs on initial visit participated in this study. Dizziness Handicap Inventory (DHI) questionnaires were completed before CRPs. All study populations were divided into three groups after successful CRPs on the initial visit day: the medication (V) group (treated with a vestibular suppressant [dimenhydrinate 50 mg per day]), the placebo (P) group, and the no medication (N) group. One week after successful CRPs, residual symptoms were checked and repeated DHI questionnaires were completed to compare residual symptoms.
RESULTS
Among the 138 patients who did not show positional nystagmus at follow-up, 67 (48.5%) complained of residual symptoms. The presence of residual symptoms was more prevalent in the P and N group compared with the V group (P = .035, P = .017, respectively). The most frequent residual symptom was lightheadedness (n = 42). Moreover, in the V group, lightheadedness was significantly reduced compared with the P group (P = .029). However, in the analysis of DHI, total and subscale scores did not differ across the three groups before or after successful CRP.
CONCLUSIONS
Vestibular suppressants significantly reduced residual symptoms compared to both placebo and no medication after CRP. However, there was no significant reduction in DHI score compared with the control group, suggesting that the residual symptoms could not be evaluated by DHI score alone.
Topics: Adult; Aged; Aged, 80 and over; Antiemetics; Benign Paroxysmal Positional Vertigo; Dimenhydrinate; Dizziness; Dose-Response Relationship, Drug; Female; Follow-Up Studies; Humans; Male; Middle Aged; Nystagmus, Physiologic; Otologic Surgical Procedures; Patient Positioning; Postoperative Complications; Retrospective Studies; Semicircular Canals; Surveys and Questionnaires; Treatment Outcome; Vestibular Function Tests; Vestibule, Labyrinth; Young Adult
PubMed: 24782447
DOI: 10.1002/lary.24741 -
Pharmacognosy Magazine 2015Since antiquity, Zingiber officinale (ginger), pogostemonis herba, and radix aucklandiae have been used as traditional Chinese medicines to remit gastrointestinal...
BACKGROUND
Since antiquity, Zingiber officinale (ginger), pogostemonis herba, and radix aucklandiae have been used as traditional Chinese medicines to remit gastrointestinal discomfort. Recent evidences also show the efficacy of the three herbal medicines against nausea and vomiting.
OBJECTIVE
To optimize the CO2 supercritical fluid extraction (SFE-CO2) conditions for ginger and the ethanol reflux extraction conditions for radix aucklandiae, control the quality of pogostemonis herba essential oil, and evaluate anti-motion sickness activity of the compound recipes composed of the three herbal medicine extracts.
MATERIALS AND METHODS
Two orthogonal array designs L9 (3)(4) were employed to optimize the SFE-CO2 conditions for enhancing yield of 6-gingerol from ginger and the ethanol reflux extraction conditions for enhancing yield of costunolide and dehydrocostus lactone from radix aucklandiae; a uniform design U5(5(3)) was applied for evaluation of anti-motion sickness activity of the compound recipes.
RESULTS
Extraction pressure (P < 0.01), extraction temperature and extraction time (P < 0.05) have significant effects on the yield of 6-gingerol from ginger by SFE-CO2; ethanol concentration (P < 0.01) and times of repeating extraction (P < 0.05) have significant effects on the total yield of costunolide and dehydrocostus lactone from radix aucklandiae by ethanol reflux extraction; the anti-motion sickness effects of the optimized compound recipe composed of the three herbal medicine extracts were markedly better than those of dimenhydrinate.
CONCLUSION
The compound recipe composed of ginger, pogostemonis herba, and radix aucklandiae could be developed as a promising anti-motion sickness medicine.
PubMed: 26246716
DOI: 10.4103/0973-1296.160444 -
European Journal of Pharmaceutics and... Nov 2014Two important driving forces for oral absorption of active pharmaceutical ingredients are drug dissolution and permeability in the gastrointestinal tract. Poorly soluble...
Two important driving forces for oral absorption of active pharmaceutical ingredients are drug dissolution and permeability in the gastrointestinal tract. Poorly soluble weak bases typically exhibit high solubility under fasted gastric conditions. However, the solubility of such drugs usually decreases drastically in the fasted small intestine, constraining drug absorption. Since there is a discrepancy in solubility between the fasted state stomach and intestine, it is crucial to examine the influence of dissolution, supersaturation and precipitation on the oral absorption of poorly soluble weak bases during and after fasted state gastric emptying. Cinnarizine is a poorly soluble weak base with borderline permeability, exhibiting supersaturation and precipitation under simulated fasted state gastric emptying conditions. Interestingly, supersaturation and precipitation of cinnarizine under fed state conditions is not expected to occur, since the drug shows good solubility in fed state biorelevant media and exhibits a positive food effect in pharmacokinetic studies. The present work is aimed at investigating the dissolution, supersaturation and precipitation behavior of marketed cinnarizine tablets under fasted and fed state conditions using biorelevant dissolution and transfer methods. In order to predict the in vivo performance of these cinnarizine formulations, the in vitro results were then coupled with different physiologically based pharmacokinetic (PBPK) models, which considered either only dissolution or a combination of dissolution, supersaturation and precipitation kinetics. The results of the in silico predictions were then compared with in vivo observations. The study revealed that under fasting conditions, plasma profiles could be accurately predicted only when supersaturation and precipitation as well as dissolution were taken into account. It was concluded that for poorly soluble weak bases with moderate permeability, supersaturation and precipitation during fasted state gastric emptying may have an essential influence on oral drug absorption and thus on in vivo drug performance.
Topics: Administration, Oral; Cinnarizine; Dimenhydrinate; Drug Combinations; Forecasting; Gastrointestinal Absorption; Humans; Male; Permeability; Solubility
PubMed: 25195981
DOI: 10.1016/j.ejpb.2014.08.011 -
Clinical Drug Investigation Jan 2020
Topics: Betahistine; Cinnarizine; Dimenhydrinate; Double-Blind Method; Humans; Prospective Studies; Vertigo
PubMed: 31679119
DOI: 10.1007/s40261-019-00872-8