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Advances in Pharmacological and... 2023Nausea and vomiting are symptoms associated with a lot of diseases and oral tablets may be unprofitable for patients especially those suffering from nausea and vomiting....
Nausea and vomiting are symptoms associated with a lot of diseases and oral tablets may be unprofitable for patients especially those suffering from nausea and vomiting. Therefore, this study aimed to formulate a new meclizine and pyridoxine combination formula for chewable tablets and provide rapid drug absorption and decrease motion sickness. The new chewable formulation has been prepared to provide fast action, is more acceptable, and could be used for all age categories. Seven trials haves been carried out to prepare to find the suitable one where formula 7 of the chewable gum preparation exhibited good taste and hardness, while the gelatin formulation give an accepted formula after four trials with better taste and good acceptance. The prepared formulations give a dissolution profile of meclizine (95.53-102.8%) and pyridoxine (99.25 ± 115%) and assay (98 + 0.05-99.3 ± 0.8%) for meclizine and (97 ± 0.9-100.0 ± 0.08%) for the pyridoxine in three prepared formulations of chewable tablets. Followed by the evaluation, the formulation and testing them on human volunteers are carried out to confirm their effect to ensure acceptance and fast actions. The finding is promising for preparing a new route of administration of meclizine and pyridoxine combination to be used in the market.
PubMed: 37547166
DOI: 10.1155/2023/5512379 -
Molecular Endocrinology (Baltimore, Md.) Oct 2004The constitutive androstane receptor (CAR, NR1I3) is a key regulator of xenobiotic and endobiotic metabolism. The ligand-binding domains of murine (m) and human (h) CAR...
The constitutive androstane receptor (CAR, NR1I3) is a key regulator of xenobiotic and endobiotic metabolism. The ligand-binding domains of murine (m) and human (h) CAR are divergent relative to other nuclear hormone receptors, resulting in species-specific differences in xenobiotic responses. Here we identify the widely used antiemetic meclizine (Antivert; Bonine) as both an agonist ligand for mCAR and an inverse agonist for hCAR. Meclizine increases mCAR transactivation in a dose-dependent manner. Like the mCAR agonist 1,4-bis[2-(3,5-dichloropyridyloxy)]benzene, meclizine stimulates binding of steroid receptor coactivator 1 to the murine receptor in vitro. Meclizine administration to mice increases expression of CAR target genes in a CAR-dependent manner. In contrast, meclizine suppresses hCAR transactivation and inhibits the phenobarbital-induced expression of the CAR target genes, cytochrome p450 monooxygenase (CYP)2B10, CYP3A11, and CYP1A2, in primary hepatocytes derived from mice expressing hCAR, but not mCAR. The inhibitory effect of meclizine also suppresses acetaminophen-induced liver toxicity in humanized CAR mice. These results demonstrate that a single compound can induce opposite xenobiotic responses via orthologous receptors in rodents and humans.
Topics: Animals; Antiemetics; Cell Line, Tumor; Cells, Cultured; Constitutive Androstane Receptor; Hepatocytes; Humans; Meclizine; Mice; Mice, Knockout; RNA; Receptors, Cytoplasmic and Nuclear; Recombinant Proteins; Transcription Factors; Transfection
PubMed: 15272053
DOI: 10.1210/me.2004-0046 -
Drug Development and Industrial Pharmacy Mar 2021An enantiomeric separation of meclizine enantiomers by liquid chromatography with tandem mass spectrometry LC-MS method was developed and validated for the analysis of...
An enantiomeric separation of meclizine enantiomers by liquid chromatography with tandem mass spectrometry LC-MS method was developed and validated for the analysis of Meclizine enantiomers. Enantiomeric resolution of the drug products were successfully achieved on a Phenomenex® lux cellulose 1 C18 (250 mm × 4.6 mm i.d, 5 µm particle size) column with mobile phase consisting of acetonitrile: 5 mM ammonium format pH (5.5) adjusted with formic acid (90:10) (v/v), and a flow rate of 0.4 mL/min. The developed method provided linear responses within the concentration range 1-5 ng/mL, and regression analysis showed a correlation coefficient value (r) of 0.999. The optimized mobile phase separated (+) Meclizine at 1.58 min and (-) Meclizine at 2.20 min, respectively. The LC/MS method was validated as per ICH guidelines with respect to specificity, precision, linearity and robustness. Limit of detection (LOD) and limit of quantification (LOQ) were found to be 1.0 ng/mL and 5.0 ng/mL respectively. The proposed method is suitable for analysis of meclizine enantiomers in pharmaceutical formulations and quality control analysis.
Topics: Chromatography, High Pressure Liquid; Chromatography, Liquid; Drug Compounding; Meclizine; Reproducibility of Results; Stereoisomerism; Tandem Mass Spectrometry
PubMed: 33291999
DOI: 10.1080/03639045.2020.1862174 -
Frontiers in Pharmacology 2017[This corrects the article on p. 693 in vol. 8, PMID: 29046637.].
[This corrects the article on p. 693 in vol. 8, PMID: 29046637.].
PubMed: 29377038
DOI: 10.3389/fphar.2017.00991 -
Renal Failure Dec 2023Podocytes play a critical role in maintaining normal glomerular filtration, and podocyte loss from the glomerular basement membrane (GBM) initiates and worsens chronic...
Podocytes play a critical role in maintaining normal glomerular filtration, and podocyte loss from the glomerular basement membrane (GBM) initiates and worsens chronic kidney disease (CKD). However, the exact mechanism underlying podocyte loss remains unclear. Fructose-2,6-biphosphatase 3 (PFKFB3) is a bifunctional enzyme that plays crucial roles in glycolysis, cell proliferation, cell survival, and cell adhesion. This study aimed to determine the role of PFKFB3 in angiotensin II (Ang II) kidney damage. We found that mice infused with Ang II developed glomerular podocyte detachment and impaired renal function accompanied by decreased PFKFB3 expression and . Inhibition of PFKFB3 with the PFKFB3 inhibitor 3PO further aggravated podocyte loss induced by Ang II. In contrast, activating PFKFB3 with the PFKFB3 agonist meclizine alleviated the podocyte loss induced by Ang II. Mechanistically, PFKFB3 knockdown likely aggravate Ang II-induced podocyte loss by suppressing talin1 phosphorylation and integrin beta1 subunit (ITGB1) activity. Conversely, PFKFB3 overexpression protected against Ang II-induced podocyte loss. These findings suggest that Ang II leads to a decrease in podocyte adhesion by suppressing PFKFB3 expression, and indicates a potential therapeutic target for podocyte injury in CKD.
Topics: Animals; Mice; Angiotensin II; Down-Regulation; Phosphorylation; Podocytes; Renal Insufficiency, Chronic; Phosphofructokinase-2
PubMed: 37427767
DOI: 10.1080/0886022X.2023.2230318 -
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 -
British Medical Journal Feb 1978
Topics: Abnormalities, Drug-Induced; Child; Female; Humans; Meclizine; Pregnancy
PubMed: 626846
DOI: 10.1136/bmj.1.6111.483 -
Nature Reviews. Disease Primers May 2016Meniere's disease (MD) is a disorder of the inner ear that causes vertigo attacks, fluctuating hearing loss, tinnitus and aural fullness. The aetiology of MD is... (Review)
Review
Meniere's disease (MD) is a disorder of the inner ear that causes vertigo attacks, fluctuating hearing loss, tinnitus and aural fullness. The aetiology of MD is multifactorial. A characteristic sign of MD is endolymphatic hydrops (EH), a disorder in which excessive endolymph accumulates in the inner ear and causes damage to the ganglion cells. In most patients, the clinical symptoms of MD present after considerable accumulation of endolymph has occurred. However, some patients develop symptoms in the early stages of EH. The reason for the variability in the symptomatology is unknown and the relationship between EH and the clinical symptoms of MD requires further study. The diagnosis of MD is based on clinical symptoms but can be complemented with functional inner ear tests, including audiometry, vestibular-evoked myogenic potential testing, caloric testing, electrocochleography or head impulse tests. MRI has been optimized to directly visualize EH in the cochlea, vestibule and semicircular canals, and its use is shifting from the research setting to the clinic. The management of MD is mainly aimed at the relief of acute attacks of vertigo and the prevention of recurrent attacks. Therapeutic options are based on empirical evidence and include the management of risk factors and a conservative approach as the first line of treatment. When medical treatment is unable to suppress vertigo attacks, intratympanic gentamicin therapy or endolymphatic sac decompression surgery is usually considered. This Primer covers the pathophysiology, symptomatology, diagnosis, management, quality of life and prevention of MD.
Topics: Antiemetics; Audiometry; Benzodiazepines; Catheter Ablation; Dimenhydrinate; Ear, Inner; Endolymph; Ganglia, Sensory; Hearing Loss; Humans; Magnetic Resonance Imaging; Meclizine; Meniere Disease; Promethazine; Quality of Life; Tinnitus; Vertigo
PubMed: 27170253
DOI: 10.1038/nrdp.2016.28 -
Svenska Lakartidningen Apr 1964
Topics: Abnormalities, Drug-Induced; Meclizine; Pregnancy; Statistics as Topic; Sweden; Toxicology
PubMed: 14145141
DOI: No ID Found -
PloS One 2020Achondroplasia (ACH) is the most common short-limbed skeletal dysplasia caused by activating mutations in the fibroblast growth factor receptor 3 (FGFR3) gene. We...
Achondroplasia (ACH) is the most common short-limbed skeletal dysplasia caused by activating mutations in the fibroblast growth factor receptor 3 (FGFR3) gene. We identified that meclizine hydrochloride inhibited FGFR3 signaling in various chondrocytic cells and promoted longitudinal bone growth in mouse model of ACH. Meclizine has safely been used for more than 50 years, but it lacks the safety data for repeated administration and pharmacokinetics (PK) when administered to children. We performed a phase Ia study to evaluate the PK and safety of meclizine administered orally to ACH children. Twelve ACH children aged from 5 to younger than 11 years were recruited, and the first 6 subjects received once a day of meclizine in the fasted condition, subsequent 6 subjects received twice a day of meclizine in the fed condition. Meclizine was well tolerated in ACH children with no serious adverse events. The mean Cmax, Tmax, AUC0-24h, t1/2 during 24 hours in the fasted condition were 130 ng/mL, 1.7 hours, 761 ng·h/mL, and 8.5 hours respectively. The simulation of repeated administration of meclizine for 14 days demonstrated that plasma concentration apparently reached steady state around 10 days after the first dose both at once a day and twice a day administration. The AUC0-10h of the fasting and fed condition were 504 ng·h/mL and 813 ng·h/mL, respectively, indicating exposure of meclizine increased with the diet. Although higher drug exposure was confirmed in ACH children compared to adults, a single administration of meclizine seemed to be well tolerated.
Topics: Achondroplasia; Administration, Oral; Animals; Child; Child, Preschool; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Humans; Male; Meclizine; Mice; Pharmacokinetics
PubMed: 32282831
DOI: 10.1371/journal.pone.0229639