-
EBioMedicine Sep 2015
Topics: Acute Kidney Injury; Animals; Kidney; Male; Meclizine; Mice; Reperfusion Injury
PubMed: 26501091
DOI: 10.1016/j.ebiom.2015.09.016 -
The Consultant Pharmacist : the Journal... Apr 2015Few studies have examined racial differences in potentially inappropriate medication use. The objective of this study was to examine racial disparities in using...
OBJECTIVE
Few studies have examined racial differences in potentially inappropriate medication use. The objective of this study was to examine racial disparities in using prescription and/or nonprescription anticholinergics, a type of potentially inappropriate medication, over time.
DESIGN
Longitudinal.
SETTING
Data from the Health, Aging, and Body Composition Study (years 1, 5, and 10).
PARTICIPANTS
Three thousand fifty-five community-dwelling older adults, both blacks and whites, at year 1.
MAIN OUTCOME MEASURE
Highly anticholinergic medication use per the 2012 American Geriatrics Society Updated Beers Criteria for Potentially Inappropriate Medication Use in Older Adults.
RESULTS
Blacks represented 41.4% of the participants at year 1. At year 1, 13.4% of blacks used an anticholinergic medication compared with 17.8% of whites, and this difference persisted over the ensuing 10-year period. Diphenhydramine was the most common anticholinergic medication reported at baseline and year 5, and meclizine at year 10, for both races. Controlling for demographics, health status, and access to care factors, blacks were 24% to 45% less likely to use any anticholinergics compared with whites over the years considered (all P < 0.05).
CONCLUSION
The use of prescription and/or nonprescription anticholinergic medications was less common in older blacks than whites over a 10-year period, and the difference was unexplained by demographics, health status, and access to care.
Topics: Aged; Black People; Cholinergic Antagonists; Drug Utilization; Female; Humans; Male; White People
PubMed: 25893702
DOI: 10.4140/TCP.n.2015.240 -
AAPS PharmSciTech Oct 2015
Topics: Administration, Oral; Biological Availability; Dextromethorphan; Guaifenesin; Humans; Hydrogen-Ion Concentration; Meclizine; Nonprescription Drugs; Phenazopyridine; Solubility; Technology, Pharmaceutical
PubMed: 25680355
DOI: 10.1208/s12249-015-0297-x -
International Scholarly Research Notices 2014The intention of present research is to formulate and develop the meclizine hydrochloride fast dissolving tablets using sublimation method to enhance the dissolution...
The intention of present research is to formulate and develop the meclizine hydrochloride fast dissolving tablets using sublimation method to enhance the dissolution rate. In this study an attempt was made to fasten the drug release from the oral tablets by incorporating the superdisintegrants and camphor as sublimating agent. The prepared fast dissolving tablets were subjected to precompression properties and characterized for hardness, weight variation, friability, wetting time, water absorption ratio, and disintegration time. From in vitro release studies, the formulation F9 exhibited fast release profile of about 98.61% in 30 min, and disintegration time 47 sec when compared with other formulations. The percent drug release in 30 min (Q 30) and initial dissolution rate for formulation F9 was 98.61 ± 0.25%, 3.29%/min. These were very much higher compared to marketed tablets (65.43 ± 0.57%, 2.18%/min). The dissolution efficiency was found to be 63.37 and it is increased by 1.4-fold with F9 FDT tablets compared to marketed tablets. Differential scanning calorimetry and Fourier transform infrared spectroscopy studies revealed that there was no possibility of interactions. Thus the development of meclizine hydrochloride fast dissolving tablets by sublimation method is a suitable approach to improve the dissolution rate.
PubMed: 27355021
DOI: 10.1155/2014/281376 -
PloS One 2013Achondroplasia (ACH) is one of the most common skeletal dysplasias with short stature caused by gain-of-function mutations in FGFR3 encoding the fibroblast growth factor...
Achondroplasia (ACH) is one of the most common skeletal dysplasias with short stature caused by gain-of-function mutations in FGFR3 encoding the fibroblast growth factor receptor 3. We used the drug repositioning strategy to identify an FDA-approved drug that suppresses abnormally activated FGFR3 signaling in ACH. We found that meclozine, an anti-histamine drug that has long been used for motion sickness, facilitates chondrocyte proliferation and mitigates loss of extracellular matrix in FGF2-treated rat chondrosarcoma (RCS) cells. Meclozine also ameliorated abnormally suppressed proliferation of human chondrosarcoma (HCS-2/8) cells that were infected with lentivirus expressing constitutively active mutants of FGFR3-K650E causing thanatophoric dysplasia, FGFR3-K650M causing SADDAN, and FGFR3-G380R causing ACH. Similarly, meclozine alleviated abnormally suppressed differentiation of ATDC5 chondrogenic cells expressing FGFR3-K650E and -G380R in micromass culture. We also confirmed that meclozine alleviates FGF2-mediated longitudinal growth inhibition of embryonic tibia in bone explant culture. Interestingly, meclozine enhanced growth of embryonic tibia in explant culture even in the absence of FGF2 treatment. Analyses of intracellular FGFR3 signaling disclosed that meclozine downregulates phosphorylation of ERK but not of MEK in FGF2-treated RCS cells. Similarly, meclozine enhanced proliferation of RCS cells expressing constitutively active mutants of MEK and RAF but not of ERK, which suggests that meclozine downregulates the FGFR3 signaling by possibly attenuating ERK phosphorylation. We used the C-natriuretic peptide (CNP) as a potent inhibitor of the FGFR3 signaling throughout our experiments, and found that meclozine was as efficient as CNP in attenuating the abnormal FGFR3 signaling. We propose that meclozine is a potential therapeutic agent for treating ACH and other FGFR3-related skeletal dysplasias.
Topics: Achondroplasia; Amino Acid Substitution; Animals; Cell Differentiation; Cell Proliferation; Cells, Cultured; Chondrocytes; Extracellular Matrix; Extracellular Signal-Regulated MAP Kinases; Fibroblast Growth Factor 2; Humans; Lentivirus; Meclizine; Models, Biological; Mutation; Phosphorylation; Rats; Receptor, Fibroblast Growth Factor, Type 3; Signal Transduction; Tibia
PubMed: 24324705
DOI: 10.1371/journal.pone.0081569 -
The Journal of Biological Chemistry Dec 2013We recently identified meclizine, an over-the-counter drug, as an inhibitor of mitochondrial respiration. Curiously, meclizine blunted respiration in intact cells but...
We recently identified meclizine, an over-the-counter drug, as an inhibitor of mitochondrial respiration. Curiously, meclizine blunted respiration in intact cells but not in isolated mitochondria, suggesting an unorthodox mechanism. Using a metabolic profiling approach, we now show that treatment with meclizine leads to a sharp elevation of cellular phosphoethanolamine, an intermediate in the ethanolamine branch of the Kennedy pathway of phosphatidylethanolamine biosynthesis. Metabolic labeling and in vitro enzyme assays confirmed direct inhibition of the cytosolic enzyme CTP:phosphoethanolamine cytidylyltransferase (PCYT2). Inhibition of PCYT2 by meclizine led to rapid accumulation of its substrate, phosphoethanolamine, which is itself an inhibitor of mitochondrial respiration. Our work identifies the first pharmacologic inhibitor of the Kennedy pathway, demonstrates that its biosynthetic intermediate is an endogenous inhibitor of respiration, and provides key mechanistic insights that may facilitate repurposing meclizine for disorders of energy metabolism.
Topics: Animals; Antiemetics; Cell Line; Cell Respiration; Cytosol; Enzyme Inhibitors; Ethanolamines; Gene Knockdown Techniques; Humans; Meclizine; Metabolic Networks and Pathways; Mice; Mitochondria; RNA Nucleotidyltransferases
PubMed: 24142790
DOI: 10.1074/jbc.M113.489237 -
Neuropsychopharmacology : Official... Feb 2014Histamine H1 receptor systems have been shown in animal studies to have important roles in the reversal of sensorimotor gating deficits, as measured by prepulse... (Randomized Controlled Trial)
Randomized Controlled Trial
Histamine H1 receptor systems have been shown in animal studies to have important roles in the reversal of sensorimotor gating deficits, as measured by prepulse inhibition (PPI). H1-antagonist treatment attenuates the PPI impairments caused by either blockade of NMDA glutamate receptors or facilitation of dopamine transmission. The current experiment brought the investigation of H1 effects on sensorimotor gating to human studies. The effects of the histamine H1 antagonist meclizine on the startle response and PPI were investigated in healthy male subjects with high baseline startle responses and low PPI levels. Meclizine was administered to participants (n=24) using a within-subjects design with each participant receiving 0, 12.5, and 25 mg of meclizine in a counterbalanced order. Startle response, PPI, heart rate response, galvanic skin response, and changes in self-report ratings of alertness levels and affective states (arousal and valence) were assessed. When compared with the control (placebo) condition, the two doses of meclizine analyzed (12.5 and 25 mg) produced significant increases in PPI without affecting the magnitude of the startle response or other physiological variables. Meclizine also caused a significant increase in overall self-reported arousal levels, which was not correlated with the observed increase in PPI. These results are in agreement with previous reports in the animal literature and suggest that H1 antagonists may have beneficial effects in the treatment of subjects with compromised sensorimotor gating and enhanced motor responses to sensory stimuli.
Topics: Acoustic Stimulation; Adolescent; Adult; Dose-Response Relationship, Drug; Double-Blind Method; Female; Galvanic Skin Response; Heart Rate; Histamine H1 Antagonists; Humans; Male; Meclizine; Neural Inhibition; Reflex, Startle; Self Report; Sensory Gating; Young Adult
PubMed: 24045586
DOI: 10.1038/npp.2013.248 -
Pharmacological Reports : PR 2013The potential edematogenic effect and the pharmacological characterization of a glucose-mannose-binding lectin from Dioclea violacea (DvL) were investigated.
BACKGROUND
The potential edematogenic effect and the pharmacological characterization of a glucose-mannose-binding lectin from Dioclea violacea (DvL) were investigated.
METHODS
Paw edema was induced with DvL in control animals, and in animals pretreated with glucocorticoid or with blockers of histamine, nitric oxide synthase, cyclooxygenase, platelet activating factor (PAF), bradykinin and lipoxygenase.
RESULTS
DvL-induced paw edema paralleled with an increase in vascular permeability and myeloperoxidase (MPO) activity. DvL-induced edema could be prevented by pre-treatment with the lectin-binding sugar α-D-methyl mannoside. Dexamethasone, meclizine and Nω-nitro-L-arginine methyl ester hydrochloride (L-NAME) inhibited this effect.
CONCLUSIONS
DvL induces edema, increase in vascular permeability and neutrophil infiltration. The edematogenic activity involves the lectin mannose-binding sites and is associated with histamine, cytokines and nitric oxide, since it could be treated with meclizine, dexamethasone and L-NAME.
Topics: Animals; Anti-Inflammatory Agents; Binding Sites; Cytokines; Dexamethasone; Dioclea; Disease Models, Animal; Edema; Female; Histamine; Mannose-Binding Lectin; Meclizine; NG-Nitroarginine Methyl Ester; Neutrophil Infiltration; Neutrophils; Nitric Oxide; Peroxidase; Rats; Rats, Wistar
PubMed: 23563042
DOI: 10.1016/s1734-1140(13)70982-4 -
Journal of Young Pharmacists : JYP Oct 2012Meclizine HCl is a poorly water-soluble drug having a very slow-onset of action. The effect of 2-hydroxypropyl-β-cyclodextrins and β-cyclodextrins on its aqueous...
Meclizine HCl is a poorly water-soluble drug having a very slow-onset of action. The effect of 2-hydroxypropyl-β-cyclodextrins and β-cyclodextrins on its aqueous solubility and dissolution rate was investigated. The phase solubility profile indicated that the solubility of Meclizine HCl was significantly increased in the presence of both 2-hydroxypropyl-β-cyclodextrin and β- cyclodextrin; an extend of increase being more for 2-hydroxypropyl-β-cyclodextrin. It was classified as AL-type, indicating the 1:1 stoichiometric inclusion complexes. The complexes formed were quite stable. The solid complexes prepared by physical mixtures, kneading methods, and co-precipitation methods were characterized using differential scanning calorimetry and FTIR. An in vitro study showed that the solubility and dissolution rate of Meclizine HCl were significantly improved by complexation with 2-hydroxypropyl-β-cyclodextrin. Tablet formulation using 1:1 kneading complex of Meclizine HCl and 2-hydroxypropyl-β-cyclodextrin with drug equivalent to 25 mg was prepared by a direct compression method. A dissolution study of prepared tablets was performed in 0.5% SLS in water (pH 7.0). Almost 96% drug was released from the formulation at the end of 30min. A comparison study of prepared tablets was done with marketed a Meclizine HCl 25 mg conventional tablet. From the results of dissolution study, it was found that the prepared formulation was showing better release, which was statistically significant P < 0.01 than a marketed tablet (paired t-test). Only 54% drug release was observed from the marketed tablet at the end of 30 min. Hence this study concludes that the solubility enhancement of Meclizine HCl could be successfully achieved using the inclusion complexation technique.
PubMed: 23493156
DOI: 10.4103/0975-1483.104365 -
The Journal of Biological Chemistry Mar 2013PGC-1-related coactivator (PRC), a growth-regulated member of the PGC-1 coactivator family, contributes to the expression of the mitochondrial respiratory apparatus. PRC...
PGC-1-related coactivator (PRC), a growth-regulated member of the PGC-1 coactivator family, contributes to the expression of the mitochondrial respiratory apparatus. PRC also orchestrates a robust response to metabolic stress by promoting the expression of multiple genes specifying inflammation, proliferation, and metabolic reprogramming. Here, we demonstrate that this PRC-dependent stress program is activated during apoptosis and senescence, two major protective mechanisms against cellular dysfunction. Both PRC and its targets (IL1α, SPRR2D, and SPRR2F) were rapidly induced by menadione, an agent that promotes apoptosis through the generation of intracellular oxidants. Menadione-induced apoptosis and the PRC stress program were blocked by the antioxidant N-acetylcysteine. The PRC stress response was also activated by the topoisomerase I inhibitor 7-ethyl-10-hydroxycamptothecin (SN-38), an inducer of premature senescence in tumor cells. Cells treated with SN-38 displayed morphological characteristics of senescence and express senescence-associated β-galactosidase activity. In contrast to menadione, the SN-38 induction of the PRC program occurred over an extended time course and was antioxidant-insensitive. The potential adaptive function of the PRC stress response was investigated by treating cells with meclizine, a drug that promotes glycolytic energy metabolism and has been linked to cardio- and neuroprotection against ischemia-reperfusion injury. Meclizine increased lactate production and was a potent inducer of the PRC stress program, suggesting that PRC may contribute to the protective effects of meclizine. Finally, c-MYC and PRC were coordinately induced under all conditions tested, implicating c-MYC in the biological response to metabolic stress. The results suggest a general role for PRC in the adaptive response to cellular dysfunction.
Topics: Acetylcysteine; Antioxidants; Apoptosis; Camptothecin; Carbonyl Cyanide m-Chlorophenyl Hydrazone; Cell Line, Tumor; Cell Survival; Cellular Senescence; Cornified Envelope Proline-Rich Proteins; Gene Expression; Gene Knockdown Techniques; Histamine H1 Antagonists; Humans; Inflammation; Irinotecan; Kinetics; Meclizine; Oxidants; Oxidative Stress; Proto-Oncogene Proteins c-myc; Proton Ionophores; RNA, Small Interfering; Topoisomerase I Inhibitors; Transcription Factors; Transcriptional Activation; Vitamin K 3
PubMed: 23364789
DOI: 10.1074/jbc.M112.426841